Nanomaterial-enabled drug transport systems: a comprehensive exploration of current developments and future avenues in therapeutic delivery

Abstract

Over the years, nanotechnology has gained popularity as a viable solution to address gene and drug delivery challenges over conventional methods. Extensive research has been conducted on nanosystems that consist of organic/inorganic materials, drugs, and its biocompatibility become the primary goal of improving drug delivery. Various surface modification methods help focus targeted and controlled drug release, further enabling multidrug delivery also. This newer technology ensures the stability of drugs that can unravel the mechanisms involved in cellular processes of disease development and its management. Tailored medication delivery provides benefits such as therapy, controlled release, and reduced adverse effects, which are especially important for controlling illnesses like cancer. However, multifunctional nanocarriers that possess high viscoelasticity, extended circulation half-life, biocompatibility, and biodegradability face some challenges and limitations too in human bodies. To produce a consistent therapeutic platform based on complex three-dimensional nanoparticles, careful design and engineering, thorough orthogonal analysis methods, and reproducible scale-up and manufacturing processes will be required in the future. Safety and effectiveness of nano-based drug delivery should be thoroughly investigated in preclinical and clinical trials, especially when considering biodistribution, targeting specific areas, and potential immunological toxicities. Overall, the current review article explores the advancements in nanotechnology, specific to nanomaterial-enabled drug delivery systems, carrier fabrication techniques and modifications, disease management, clinical research, applications, limitations, and future challenges. The work portrays how nanomedicine distribution affects healthcare with an emphasis on the developments in drug delivery techniques.

Introduction

Understanding and manipulating matter at dimensions between 1 and 100 nm, where special phenomena allow for fresh applications, is referred as nanotechnology (Bayda et al. 2020). Norio Taniguchi, a Japanese scientist was attributed to be the first to coin the term “Nanotechnology” that describes semiconductor process occurred at the order of a nanometre scale. He sponsored that nanotechnology encompassed of processing, separation, consolidation, and deformation of materials by one atom or one molecule (Hulla et al. 2015). Afterwards, it appeared in the late 1960s, where nanotechnology defines—a combination of basic chemistry, biology, and technology and that shook the globe and left everyone in a state of confusion. Using the unique characteristics of atomic and molecular assemblages constructed at the nanoscale, nowadays researchers have used nanotechnology into one of the most significant scientific achievements of the early twenty-first century. Nanotechnology in the present world investigates phenomena and material manipulation at the macromolecular, molecular, and atomic dimensions, where properties are vastly different from those at larger scales and pose advantages (Bayda et al. 2020).

Among many other application areas, nanomaterials are used extensively in medical research (Patra et al. 2017). Numerous products, including filter media, tissue engineering, reinforcement in nanocomposites, and micro- or nano-electromechanical systems, utilize nanofibers manufactured from a variety of materials, including carbon, polymers, and semiconductors (Cao et al. 2007; Kinnear et al. 2017; Weissig et al. 2014). Nanomaterials offer a solution by encapsulating drugs improving solubility and increasing bioavailability. Additionally, sensitive drugs enclosed within nanomaterials gain protection, against degradation enhancing their stability and prolonging their shelf life. Accurate drug targeting plays a role, in therapy aiming to minimize effects and maximize effectiveness (Bhushan et al. 2017). Nanotechnology presents a solution, with its ability to precisely target cells through surface modifications of nanomaterials. By modifying the nanomaterials, they can identify molecules or receptors on the target cells guiding the drug directly to its intended destination. This targeted approach minimizes harm to tissues, resulting in better treatment, and reduced overall toxicity (Yuan et al. 2019).

In the majority of these applications, the nanofibers are subject to stresses and strains from the surrounding medium throughout their service life. The nanofibers may fail or undergo irreversible distortion as a result of such forces. Therefore, it is necessary to describe the mechanical characteristics of individual nanofibers. The practical method for creating nanofibers, among many other techniques is electrospinning (Mirjalili and Zohoori 2016). It has recently been shown that electrospinning, which involves electrostatic forces to spin strands, is capable of creating fibers with a submicron diameter. Rayleigh made the initial observation of the electrospinning process in 1897, and Zeleny began a thorough investigation of it in the early 1900s. However, it was not until 1934, following Formhals’ invention, that electrospinning became a practical method for producing fiber with a tiny diameter. The electrospinning procedure and a device with a movable fiber collector, such as a mandrel to collect fibers in a stretched shape, were both patented by Bherdwaj and Kundu (Pillay et al. 2013).

A variety of polymeric fibers may be spun with it, which gives it versatility and reliability in creating fibers in the submicron range, electrospinning has garnered a lot of interest in the previous 10 years. In the electrospinning procedure, jets of electrically charged polymer solutions or melts are produced and the solvent is evaporated to make nanofibers. The fibers are gathered by the oppositely charged collector, which can be a spinning drum or a flat surface, and are field-directed toward the highly charged fibers. Tensile, gravitational, aerodynamic, rheological, and inertial stresses are all applied to the fiber during standard conventional spinning procedures. The primary process for spinning the fibers in electrospinning is the production of tensile forces by the charges produced when an electric field is present in the axial direction of the polymer’s flow (Subbiah et al. 2005).

For a variety of applications, including cancer therapy, anti-bacterial sheets, and tissue scaffolds, electrospun nanofiber-based drug delivery systems have been developed recently (Lee et al. 2012; Yuan et al. 2019). To accomplish the intended therapeutic effects, nanofiber-based drug-delivery devices are broadly applicable for precise drug release depending on target location and timing. The proper drug delivery mechanism is necessary for a medication to ensure its precise release profile and produce the intended therapeutic effect. A drug's release must be coordinated with its therapeutic target as nearly as feasible in terms of its location, time, and pace (Kajdič et al 2019).

This article delves into the captivating world of nanotechnology, in drug delivery uncovering its benefits and potential for patients. They can be engineered to carry compounds and safely transport them to locations within the body while protecting them from degradation (Emerich and Thanos 2003). Various types of nanomaterials including liposomes, polymeric nanomaterials, dendrimers, and carbon nanotubes have been used extensively A significant challenge in drug development lies in ensuring the solubility and stability of ingredients.

Nanomaterials-based drug delivery

The field of healthcare has witnessed advancements in the realm of nanotechnology offering possibilities to revolutionize drug delivery (Fig. 1). Scientists are exploring the potential of nanomaterials to administer medications with improved precision, effectiveness, and fewer side effects (Hulla et al. 2015). Nanomaterials have the potential to release medications in a controlled manner ensuring that the therapeutic effect is sustained and optimal (Malik et al. 2023). By manipulating factors, like size, shape, and surface properties of nanoparticles scientists can achieve patterns of drug release. This controlled release approach reduces the need of repeated dosing and also improves adherence to the treatment and maintains drug levels within the desired range for a longer duration. In the body, there are natural barriers that hinder efficient drug delivery (Salem 2023), nanoparticles can navigate through these barriers enhancing drug permeability and availability in the body. For example, they can cross the blood–brain barrier (BBB) and deliver therapeutics to the nervous system, moreover, nanoparticles can overcome obstacles presented by cell membranes and enable targeted delivery of drugs inside cells. Nanotechnology also plays a role in imaging and diagnostics (Rawat et al. 2023). Scientists can engineer nanoparticles to carry contrast agents or fluorescent dyes that improve the visualization of tumors, infections, or specific biomarkers. This imaging capability aids in the detection of diseases, precise diagnosis, and effective monitoring—enabling interventions. Although nanotechnology holds promise, for drug delivery purposes there are still challenges that need attention. The BBB (Blood Brain Barrier) can be effectively addressed using nanotherapeutics. These nanotherapeutics have the advantage of staying in the body for a while and their release pattern can be controlled by adjusting the size and design of nanoparticles. However, one drawback is that the medication is distributed uniformly throughout the body lacking selectivity, towards targeted locations. This means that the medication can attach to both healthy cells (Kim et al. 2013) and consequently, higher medication dosages might be required at the expense of effectiveness and potential non-specific toxicity. In drug delivery, nanotechnology has introduced possibilities for the controlled release of medications (Huang et al. 2018).

Fig. 1.

Different approaches of drug delivery using nanomaterials for therapeutic applications. Nano enabled drug delivery system (DDS) is dependent on the shape, size, surface chemistry, and composition of nanomaterials

Ensuring nanomaterial safety, scalability of manufacturing processes, and regulatory considerations are areas that require research and development. However, the continuous advancements, in nanotechnology are opening doors for medicine combination therapies and the potential for the treatment of various diseases (Haris et al. 2023). Nanotechnology has significantly transformed the field of drug delivery offering opportunities to enhance treatment effectiveness while minimizing effects (Bayr 2005). By employing targeting, controlled-release mechanisms, and improved drug stability, nanoparticles are revolutionizing the administration of medications (Krumova et al. 2016). As research in this area continues to progress, we can anticipate witnessing breakthroughs that will ultimately lead to patient outcomes and reshape the future of healthcare.

Utilizing nanocarriers for vaccine delivery

The use of nanocarriers has significantly transformed vaccine delivery methods in the realm of COVID-19 (Guerrini et al. 2022). A significant breakthrough has been the innovation of nanoparticles (LNPs) for delivering mRNA vaccines (Khurana et al. 2021; Zamani et al. 2023). LNPs shield the molecules from enzymatic degradation within the body enabling safe and effective transportation of genetic material into the cells. This technological advancement has played a role in the success of vaccines like those from Pfizer BioNTech, and Moderna against COVID-19 (Khurana et al. 2021). LNPs consist of lipids structured into nanoparticles providing stability to the enclosed mRNA cargo and facilitating its entry into cells. These nanoparticles are tailored with surface modifications to target cells and improve cellular absorption ultimately resulting in a robust immune response. Furthermore, LNPs can be customized to release the mRNA payload extending expression duration and immune activation. In addition to mRNA vaccines, nanocarriers are also utilized for delivering vector-based vaccines. By encapsulating vectors within nanoparticles, the genetic material is. Its delivery to target cells is enhanced, triggering strong immune responses, against the virus. The adaptability of nanocarriers allows for the inclusion of enhancers, stabilizers, and targeting molecules, which further boost the effectiveness and safety of vaccines.

Nanocarriers in pharmaceutical delivery

In delivery, nanocarriers provide targeting, controlled release, and enhanced availability of treatments. In the treatment of COVID-19, nanotechnology plays a role in transporting medications monoclonal antibodies and other biological substances to specific locations (Prabhakar et al. 2023). Nanoparticle formulations improve drug solubility shield against breakdown and support release patterns to optimize therapeutic results. For example, nanocarriers can encase medications such as Remdesivir to enhance their pharmacokinetics and facilitate delivery to infected cells. This targeted method reduces effects. This improves drug effectiveness, especially for respiratory viral infections like COVID-19 (Khurana et al. 2021). Likewise, nanocarriers loaded with monoclonal antibodies can effectively neutralize the virus presenting a treatment approach for severe cases. Additionally, nanocarriers enable therapy by delivering multiple drugs or substances with complementary effects (Du et al. 2022). This strategy enhances treatment results, lowers drug resistance issues, and also minimizes negative side effects supporting personalized approaches in managing COVID-19.

Nanotechnologies in detection

Nanotechnology-driven diagnostics have transformed COVID-19 testing by providing methods, with high sensitivity and specificity. Nanoparticle infused biosensors like gold nanoparticles, modified with antigens or antibodies are highly effective in detecting RNA or antigens in patient samples. These biosensors display color changes emit fluorescence or generate signals when they come into contact with the target substance making it easy to quickly interpret the results. Another advanced method for COVID-19 diagnostics involves using quantum dot-based assays, a technology-driven by nanotechnology (Shahbazi et al. 2012). Quantum dots are semiconductor crystals that emit types of light when stimulated, allowing for precise identification of viral RNA or proteins. By combining quantum dots with devices or portable platforms, these assays enable spot testing essential for screening and monitoring efforts.

Moreover, innovative PCR techniques enhanced by nanomaterials have revolutionized the sensitivity and accuracy of nucleic acid amplification tests for detecting COVID-19. Nanoparticles and nanoscale carriers can boost PCR efficiency, reduce background interference and facilitate the detection of viral targets to improve diagnostic precision and speed.

Nanotechnologies in protective gear

The use of nanotechnology has significantly improved the effectiveness of gears such as masks, filters, and surface coatings, in preventing spread. The masks made from nanofibers with properties or antimicrobial coatings offer filtration against respiratory droplets and aerosols containing virus particles. These face coverings help lower the chances of breathing in or spreading viruses in places, like hospitals and public areas. Additionally, special nanotechnology coatings on personal protective equipment (PPE), medical tools and frequently touched surfaces prevent viruses from sticking and multiplying. Nanomaterial-based filters for air and heating systems also play a role in controlling air quality and reducing the spread of viruses. Although nanocarriers and nanotechnologies show promise in fighting COVID-19, some challenges need attention to make their widespread use impactful. These challenges include making production scalable navigating processes for approval addressing safety concerns related to exposure to nanomaterials and ensuring the cost-effectiveness of solutions using nanotechnology.

Future research will focus on improving the design of nanocarriers for stability compatibility with living tissues and precise targeting of areas. Advances in techniques for creating things on a scale—like microfluidics technology and 3D printing—will help produce large quantities of products based on nanotechnology. Regulatory frameworks will need to keep up with changes, in the field of using particles for purposes to guarantee that new treatments and tests are safe, effective, and available. Furthermore, it is crucial to have collaboration, among experts such as researchers, doctors, engineers, and policymakers to promote innovation, application, and integration of nanotechnology into healthcare systems worldwide. Developing infrastructure investing in education and facilitating technology transfer are steps toward establishing an adaptable healthcare network capable of addressing present and future challenges posed by infectious diseases. Nanocarriers and nanotechnologies are tools in the fight against COVID-19 with applications in vaccine administration, drug delivery, diagnostics, and protective measures. Continuous exploration, creativity, and cooperation are essential for maximizing the benefits of nanotechnology in minimizing the impact of pandemics and enhancing health security.

Targeted drug delivery

Nanomaterials play an essential role in targeted drug delivery. It is a technique that aims to increase medication concentrations in particular areas of the body. The four essential steps involved in targeted drug delivery—retaining the drug molecule in regions, evading areas precisely targeting intended sites, and releasing the drug—play a crucial role in drug development. These materials possess characteristics compared to substances due, to their increased surface area and quantum effects (Chan and Ginsburg 2011). The targeted drug delivery is of two types mainly, active targeting and passive targeting.

Active targeting

Active targeting is the process of functionalizing or modifying pharmacological careers such that the contents are only delivered to the location for which the career is designed. Active targeting may be influenced at many levels such as:

• Organ compartmentalization

• Cellular targeting

• Intercellular organelle targeting

The controlled delivery of the drug delivery system to the capillary bed of a chosen target location, organ, or tissue is known as targeting (Bazak et al. 2014). The different applications and types of active and passive targeting drug delivery can be seen in (Table 1). More concentrated and focused delivery is anticipated to result in another type of molecular recognition or response to deliver nanoparticles to the tissue of interest. Potential negative effects and less toxicity can be anticipated.

Table 1.

Comparison table between active and passive drug loading in nanomaterial-based drug delivery system with its advantages and disadvantages

Drug loading type	Method of liposome production	Advantages	Disadvantages	Cases	References
Active targeting
Nanobody conjugation	Lipid film hydration method	Provides high specificity and affinity	Limited availability of nanobodies	Nanobody-modified liposomes for targeted delivery	Liu et al. (2021)
Aptamer conjugation	Remote loading method	Offers high binding affinity and specificity	Complex synthesis and aptamer conjugation	Aptamer-modified liposomes for targeted drug delivery	Odeh et al. (2019)
Glycan conjugation	Thin-film hydration method	Enables specific targeting to glycan receptors	Limited availability of glycan ligands	Liposomes functionalized with glycans for targeted delivery	Song et al. (2009)
Viral particle conjugation	Lipid film hydration method	Enhanced cellular uptake and internalization	Potential immunogenicity of viral particles	Liposomes conjugated with viral particles for cell-specific targeting and delivery	Chatterji et al. (2004)
Protein conjugation	Reverse-phase evaporation method	Provides high binding specificity and affinity	Complex manufacturing processes	Liposomes surface-modified with proteins for targeted drug delivery and therapy	Pasut (2014)
Passive targeting
Size and charge-based targeting	Lipid film hydration method	Prolonged circulation time	Clearance by the mononuclear phagocyte system (MPS)	Liposomes of different sizes and charges for targeted delivery and accumulation in specific tissues	Gyanani and Goswami (2023)
pH-dependent targeting	pH gradient method	Selective release of drugs in acidic tumor microenvironment	pH variability among tumors	pH-sensitive liposomes for targeted drug delivery to acidic tumor microenvironments	Lee et al. (2018)
Thermosensitive targeting	Lipid film hydration method	Controlled drug release in response to temperature changes	Limited stability at physiological temperatures	Thermosensitive liposomes for targeted delivery and release in hyperthermic regions	Dicheva and Koning (2014)
Enhanced permeability and retention (EPR) effect	Lipid film hydration method	Passive accumulation in tumor tissues through leaky vasculature	Variable EPR effect among tumors	PEGylated liposomes for enhanced tumor accumulation based on the EPR effect	Greish (2010)
Mucus penetration targeting	Mucus-penetrating particle (MPP) formulation	Improved penetration through mucus barriers	Variable mucus properties among tissues	Mucus-penetrating liposomes for improved delivery to mucus-rich tissues	Prasher et al. (2022)
Hybrid liposomes	Lipid film hydration method	Combined advantages of different liposome types	Complex formulation and characterization	Hybrid liposomes for versatile drug delivery and combination therapies	Matsumoto et al. (2005)
Lipid-polymer hybrid systems	Double emulsion method	Enhanced stability and controlled release	Complex synthesis and formulation	Lipid-polymer hybrid systems for targeted and sustained drug delivery	Date et al. (2018)
Stimuli-responsive liposomes	Lipid film hydration method	Triggered release of drugs in response to specific stimuli	Limited stimuli responsiveness of certain liposome formulations	Stimuli-responsive liposomes for on-demand drug delivery	Ashrafizadeh et al. (2022)
Lipid-nanoparticle hybrids	Self-assembly or co-precipitation method	Synergistic effects of lipids and nanoparticles for improved drug loading and delivery	Potential challenges in maintaining stability and homogeneity of lipid-nanoparticle hybrids	Lipid-nanoparticle hybrids for combined therapy and imaging	Markowski et al. (2022)
Liposome-drug conjugates	Post-insertion or covalent conjugation	Enhanced stability and controlled release of conjugated drugs	Complex conjugation chemistry and potential impact on drug activity	Liposome-drug conjugates for targeted drug delivery	Eroğlu and İbrahim (2020)
Exosome-inspired liposomes	Extrusion or sonication method	Mimic natural exosomes for improved biocompatibility and cellular uptake	Challenges in isolating and purifying exosome-inspired liposomes	Exosome-inspired liposomes for drug delivery and regenerative medicine	Ma and Lin (2023)
Cationic liposomes	Reverse-phase evaporation method	Efficient encapsulation and delivery of nucleic acids	Potential cytotoxicity and limited encapsulation capacity for hydrophilic drugs	Cationic liposomes for nucleic acid delivery	Shim et al. (2013)
Fusogenic liposomes	Lipid film hydration method	Facilitate fusion with cellular membranes for enhanced drug release and intracellular delivery	Potential stability issues and premature drug release	Fusogenic liposomes for intracellular drug delivery	Kube et al. (2017)
Immunoliposomes	Post-insertion method	Targeted drug delivery to specific cells expressing corresponding receptors	Potential immunogenicity and limited availability of specific targeting ligands	Immunoliposomes for targeted therapy and imaging	Paszko and Senge (2012)
Photosensitive liposomes	Lipid film hydration method	Controlled drug release in response to light irradiation	Limited tissue penetration of light and potential phototoxicity	Photosensitive liposomes for light-triggered drug delivery	Simon et al. (2023)
Inhalable liposomes	Spray drying or nebulization method	Targeted delivery to the lungs for respiratory diseases	Challenges in particle size control and potential lung inflammation	Inhalable liposomes for pulmonary drug delivery	Ponkshe et al. (2021)
Ultrasound-triggered liposomes	Lipid film hydration method	Controlled drug release and enhanced tissue penetration through ultrasound activation	Potential instability and premature drug release under ultrasound exposure	Ultrasound-triggered liposomes for localized drug delivery	Elamir et al. (2021)
pH-sensitive fusogenic liposomes	Thin-film hydration or extrusion method	Selective release of drugs in acidic tumor microenvironment and enhanced intracellular delivery	Limited stability at physiological pH and potential premature drug release	pH-sensitive fusogenic liposomes for tumor-targeted drug delivery	Saraf and Jain (2023)
Stealth liposomes	Lipid film hydration method	Prolonged circulation time and reduced clearance by the immune system	Limited stability and potential compromised drug release due to stealth coating	Stealth liposomes for improved pharmacokinetics and reduced toxicity	Sivadasan et al. (2022)
Liposomes for gene therapy	Remote loading or sonication method	Efficient delivery of therapeutic genes to target cells	Potential immunogenicity and limited transfection efficiency	Liposomes for gene therapy and genetic disorders	Luiz et al. (2022)
Liposomes for vaccine delivery	Thin-film hydration or remote loading method	Effective antigen presentation and immune response activation	Challenges in formulation optimization and potential immune response modulation	Liposomes for vaccine delivery and immunotherapy	Marasini et al. (2017)
Magnetic liposomes	Lipid film hydration or co-precipitation method	Magnetic targeting and enhanced cellular uptake	Potential instability and altered magnetic properties upon liposome formulation	Magnetic liposomes for targeted drug delivery and imaging	Shen et al. (2019)
Liposomes for ocular drug delivery	Lipid film hydration or microemulsion method	Improved bioavailability and prolonged drug release in the eye	Limited penetration through ocular barriers and potential irritation	Liposomes for ocular drug delivery and ophthalmic diseases
Cell-penetrating liposomes	Lipid film hydration or extrusion method	Efficient delivery of cargoes into cells for intracellular therapy	Potential cytotoxicity and limited delivery efficiency in certain cell types	Cell-penetrating liposomes for intracellular drug delivery	Gao et al. (2014)
Liposomes for antimicrobial delivery	Thin-film hydration or remote loading method	Enhanced drug stability and targeted delivery to infection sites	Challenges in formulation optimization and potential development of drug resistance	Liposomes for antimicrobial therapy and infectious diseases	Vatankhah et al. (2024)
Liposomes for neurodegenerative diseases	Lipid film hydration or sonication method	Targeted drug delivery to the brain and improved therapeutic efficacy	Limited blood–brain barrier penetration and potential toxicity to neuronal cells	Liposomes for neurodegenerative diseases and brain disorders	Khot et al. (2023)
pH-responsive liposomes	pH gradient method	Selective release of drugs in response to specific pH environments	Potential pH variability in vivo and stability issues at physiological pH	pH-responsive liposomes for drug delivery and cancer therapy	Hu et al. (2020)
Liposomes for bone-targeted drug delivery	Lipid film hydration or extrusion method	Enhanced drug accumulation in bone tissues and reduced systemic toxicity	Limited bone penetration and potential interference with bone remodeling	Liposomes for bone-targeted therapy and bone disorders	Hu et al. (2022)
Liposomes for cardiovascular diseases	Thin-film hydration or remote loading method	Targeted drug delivery to the cardiovascular system for improved therapeutic outcomes	Potential off-target effects and challenges in achieving site-specific accumulation	Liposomes for cardiovascular diseases and heart failure	Skourtis et al. (2020)
Liposomes for gastrointestinal delivery	Lipid film hydration or extrusion method	Improved drug stability in the gastrointestinal tract and enhanced absorption	Challenges in maintaining liposome integrity and potential gastrointestinal side effects	Liposomes for gastrointestinal drug delivery and gut diseases	Semenova et al. (2021)
Liposomes for skin delivery	Thin-film hydration or sonication method	Enhanced drug permeation through the skin and targeted delivery to skin disorders	Limited penetration through the stratum corneum and potential skin irritation	Liposomes for transdermal drug delivery and dermatological diseases	Souto et al. (2021)
Liposomes for oral drug delivery	Lipid film hydration or co-precipitation method	Protection and improved bioavailability of orally administered drugs	Challenges in overcoming enzymatic degradation and limited drug loading capacity	Liposomes for oral drug delivery and gastrointestinal disorders	Lai et al. (2020)
Liposomes for liver-targeted delivery	Thin-film hydration or remote loading method	Specific accumulation in the liver and improved therapeutic efficacy	Potential off-target effects and limited penetration to hepatic cells	Liposomes for liver-targeted therapy and liver diseases	Li et al. (2022)
Liposomes for lung delivery	Lipid film hydration or nebulization method	Targeted delivery to the lungs and improved therapeutic outcomes	Challenges in achieving optimal particle size for deep lung penetration and potential lung inflammation	Liposomes for pulmonary drug delivery and respiratory diseases	Zaru et al. (2007)

Passive targeting

The passive targeting of medicine involves utilizing the biodistribution of the carrier, colloids, which are absorbed by the reticulo endothelial system (RES). They may be the best means of passively directing medications to the most important compartments (Hirsjarvi et al. 2011). The anatomical barrier or physiological state of the nanoparticles, along with their shape, size, and surface charge, provide the basis for passive targeting. These have an impact on the passive targeted delivery of the medication or imaging agent by increasing retention effect and permeability in tumor, inflammation, or other leaky vasculature and anatomic barrier (Basu et al. 2023). Passive targeting requires a greater dosage of the imaging agent’s medication, which might have negative side effects and toxicity. The different targeting approaches of drug delivery can be seen in (Fig. 2). The cost is substantially greater and creating the nanoparticles technically takes less work.

Fig. 2.

Schematics representation of the different types of targets assisted drug delivery to diseased cancer cells using nanoparticles. Active and passive targeting represents how drugs interact with cells in the presence of nanoparticles. Drug loaded nanoparticles, normal cells, endothelial cells, and abnormal cells are shown in different colours and graphics respectively

The specificity of nanosystems interactions, with human tissues and cells

The field of nanotechnology has opened up a world of opportunities in the field of applications in targeted drug delivery, diagnostics, and tissue engineering. It is crucial to understand how nanosystems interact specifically with tissues and cells to optimize treatment effectiveness reduce side effects and ensure safety when used in clinical settings. However, these interactions depend on various non-bonded biophysiochemical connections that gradually build the corona and then accumulate (Nel et al. 2009). This section explores the complexities of these interactions including targeting mechanisms, cellular uptake pathways, and biological responses.

Targeting mechanisms

Nanosystems used in applications often incorporate targeting elements that facilitate interactions with particular cells or tissues (Shahbazi et al. 2012). These targeting agents might be aptamers, antibodies, peptides, or tiny compounds that recognize and bind to surface receptors or biomarkers to target cells. The precision of these interactions determines the accumulation of nanocarriers or nanoparticles at the intended site improving treatment outcomes while minimizing toxicity. For instance, in cancer treatment nanocarriers modified with ligands that target tumors can deliver cancer drugs directly to cancerous cells while sparing healthy tissues. This targeted approach increases drug availability at the tumor location enhances drug uptake by cancer cells and reduces exposure, to tissues—thereby lowering effects.

Cellular uptake routes

When nanosystems interact with cells they follow pathways that depend on the characteristics of nanoparticles and the type of cell. Different mechanisms play a role in how nanoparticles are taken up by cells, including endocytosis, phagocytosis, pinocytosis, and receptor-mediated internalization. Endocytosis is a pathway, for the uptake of nanosystems with clathrin-mediated and caveolae-mediated endocytosis being common processes. Nanoparticles coated with ligands that bind to cell receptors can undergo receptor-mediated endocytosis leading to targeted internalization into cells. Additionally, factors like nanoparticle size, shape, surface charge, and surface chemistry affect how they are taken up by cells. Nanoparticles within the ideal size range (e.g., 10–100 nm) often show internalization into cells due to favorable interactions with cell membranes and efficient endocytic processes.

Biological reactions

When nanosystems interact with tissues or cells they trigger biological responses that impact their effectiveness as therapeutic agents and safety profiles. These responses include changes in signaling pathways, immune reactions, and considerations regarding toxicity. Nanoparticles can influence signaling pathways by delivering molecules like drugs or nucleic acids in a targeted manner. By targeting parts, within cells or molecules nanosystems can influence how cells work change how genes are expressed, or trigger healing responses in a way that focuses on cells. The body’s immune responses to nanosystems are crucial for their compatibility and ability to avoid causing reactions. The changes made to the surface of nanoparticles like adding PEG (polyethylene glycol coating) can help reduce reactions and make them last longer in the body by avoiding being detected and removed by the system. On the other hand, nanoparticles that stimulate the system can activate immune cells and trigger specific responses that are helpful for things like delivering vaccines or immunotherapy (Vega-Vásquez et al. 2020).

It is important to understand any effects of nanosystems to ensure they are safe for use in medical treatments. Depending on what they are made of, how much has been used and how long they have been are exposed to tissues nanoparticles can cause harm by affecting cell health causing stress on cells due to oxygen levels, or triggering inflammation. The tests on the compatibility of nanosystems with cells in lab settings and using animal models are conducted to determine whether they are safe and to resolve any dangers associated with them. The nanosystems interacting with tissues or cells is a part of using nanotechnology in medicine as it affects where treatments target in the body how they enter cells and what biological responses occur. Progress in nanotechnology allows control over these interactions which helps with delivering drugs to specific areas imaging at a molecular level regenerative treatments for damaged tissues as well, as personalized therapies. Further exploration of the processes that govern interactions, between nanosystems and cells is crucial for improving treatment results safeguarding patient well-being and realizing the benefits of nanotechnology, in the field of healthcare.

Types of drugs employed in nanomaterials based drug delivery system

There are different types of drugs that are employed in nanomaterial-based drug delivery to effectively treat a range of diseases and medical conditions. These drugs can be administered through routes including transdermal, inhalation, and intravenous methods. Each drug type and its specific delivery method offer benefits that make them suitable, for therapeutic purposes (Roco 2011). Some drugs used in nanomaterial-based drug delivery and their applications are listed below with proper elaboration.

Antibiotics

Antibiotics are a class of medications utilized to combat infections. They play a role in treating a variety of diseases ranging from common ear and sinus infections to life-threatening conditions like sepsis. Antibiotics work by either killing bacteria (bactericidal) or inhibiting their growth (bacteriostatic). The effectiveness depends on the antibiotic used and the targeted bacteria species (Singh et al. 2016). For example, Amoxicillin is a prescribed antibiotic belonging to the penicillin group. It is commonly recommended for treating infections such as otitis media (ear infections) strep throat and urinary tract infections. One notable advantage of antibiotics is their administration capability, which ensures accessibility, for patients. Additionally, these medications come in forms, like tablets, capsules, and syrups which offer flexibility in dosing and ease of use.

Pain relievers

They are also called analgesics are drugs used to alleviate pain of intensities. They can act on either the system (non-opioids) or the central nervous system (opioids). The analgesics play a role in providing relief to patients with injuries, chronic conditions, or post-operative pain (Su et al. 2018). For instance, fentanyl is an opioid analgesic commonly administered through transdermal patches. It is prescribed for managing pain in cancer patients or individuals with musculoskeletal conditions. One advantage of using patches is that they ensure a controlled and consistent release of the analgesic over a period. This helps maintain pain relief without the need, for dosing while minimizing potential side effects associated with oral administration.

Antineoplastic drugs

They are also known as chemotherapy agents well are medications used to treat cancer by inhibiting the growth and spread of cancer cells. These drugs are specifically designed to target cells that rapidly divide. A feature of cancer cells (Mills and Needham 1999). For example; Paclitaxel, a used cancer medication is effective, in treating breast, ovarian, and lung cancers. It works by disrupting the process of cell division ultimately resulting in the demise of cancer cells. Advantages of chemotherapy drugs can be administered through methods such as infusions or oral tablets. This flexibility allows for treatment plans based on the type and stage of cancer. Furthermore, chemotherapy plays a role in reducing tumor size to surgery or radiation therapy.

Antiviral drugs

Specifically designed to combat infections antiviral drugs target components or processes necessary for viral replication. They are instrumental in treating infections like influenza, HIV, herpes, and hepatitis (Kumari et al. 2016). For example, Acyclovir is a medication used to treat herpes simplex virus infections including genital herpes and cold sores. The advantages of antiviral drugs can be alleviated through the severity of infections, and recovery time and inhibit the virus from multiplying and spreading within the body. They are particularly significant for individuals with weakened systems who are more vulnerable to viral infections.

Hormones

They act as chemical messengers within our body and sometimes can regulate physiological functions. Hormone replacement therapy (HRT) is a treatment that involves using hormones to address deficiencies or imbalances, in the body (Bae and Park 2011). For instance, estrogen and progesterone-based hormone therapies are commonly prescribed to postmenopausal women for relieving menopause symptoms such as flashes, night sweats, and vaginal dryness. One of the advantages of using transdermal hormone patches is that they provide a controlled and gradual release of hormones into the bloodstream closely resembling the body’s natural hormone levels. This approach helps alleviate menopause symptoms while reducing the risks associated with hormone therapy.

Immunosuppressants

This refers to medications that are utilized to suppress the activity of the system. They play a role in preventing organ rejection after transplantation and managing autoimmune diseases, where the immune system mistakenly attacks cells (Freeman et al. 1986). An example of a drug commonly used post-transplantation is cyclosporine. Its purpose is to prevent the recipient’s system from attacking the organ. The advantages of immunosuppressants lie in their ability to reduce rejection risks and increase graft survival rates after organ transplantation. In cases of diseases, these medications aid in symptom management and help prevent further damage to tissues and organs.

Bronchodilators

These are medications designed to relax airway muscles and widen air passages within the lungs facilitating airflow. They play a role in the treatment of conditions, like asthma, chronic obstructive pulmonary disease (COPD), and bronchitis. For example, salbutamol (albuterol) is a used bronchodilator that is administered through inhalation. It provides relief from asthma symptoms. Helps open up the airways during acute exacerbations. One advantage of using inhalation delivery for bronchodilators is that it allows the medication to directly reach the lungs. This leads to action. It reduces systemic side effects. This method is particularly beneficial during asthma attacks when immediate relief is necessary.

Types of diseases cured in nanomaterials based drug delivery system

An interesting approach employed by nanotechnology involves utilizing reactive oxygen species (ROS) to trigger drug release, thereby enhancing both the efficacy and safety of interventions as explored by (Betancourt et al. 2009). ROS, such, as hydrogen peroxide (H₂O₂) and superoxide radicals (O²*) are molecules in the body and play important roles in various physiological processes. The researchers have ingeniously designed nanoparticles to utilize ROS for drug release (Park 2007). This innovative strategy ensures that drugs are targeted to appropriate locations. ROS-responsive nanoparticles are specifically engineered to respond to the ROS environment found in disease sites like tumors or inflamed tissues (Saini et al. 2010). These nanoparticles typically consist of a polymer matrix. Liposomes are integrated with special components that react to ROS. When exposed to hydrogen peroxide or other types of ROS these components undergo chemical changes or degradation. This interaction with ROS triggers modifications, in the nanoparticle structure or degradation of the polymer matrix (Depan et al. 2011). Consequently, the drugs encapsulated within the nanoparticles are released in a controlled and precisely targeted manner. This drug release mechanism activated by ROS ensures that therapeutic drugs are delivered to the area maximizing their effectiveness while minimizing any unintended effects on healthy tissues.

Cancer

Cancer continues to be a major challenge to overcome affecting millions of people worldwide. Although traditional chemotherapy is effective it often causes side effects because it cannot distinguish between cancerous cells. However, drug-delivery systems have evolved to tackle this challenge by specifically targeting cancer cells. For instance, there are nanoparticle-based platforms that encapsulate chemotherapy drugs and release them directly at the site of the tumor. These nanoparticles are designed to take advantage of characteristics found in tumors such as their vasculature. As a result, nanoparticles accumulate passively within the tumor while sparing tissues. By minimizing exposure to cells this approach significantly reduces effects, like nausea, hair loss, and weakened immune system response hence patients undergoing chemotherapy may experience reduced discomfort (Jaiswal et al. 2016). When it comes to diabetes management, it is essential to prevent complications. Many individuals with diabetes rely on insulin injections, which can be inconvenient and uncomfortable; however, there have been advancements in drug delivery methods that introduce insulin pumps of automatically deliver insulin based on real time glucose monitoring. These pumps eliminate the need for injections providing relief from the constant burden of managing diabetes (Handa et al. 2023). These pumps accurately regulate blood glucose levels lowering the risks associated with hyperglycemia and hypoglycemia. Consequently, the patients can lead active lives without worrying about fluctuations in their blood sugar levels that could have restricted their daily activities and overall well-being.

Improving drug stability and effectiveness

Utilizing nanomaterials, in drug delivery systems enhances the stability and effectiveness of chemotherapy medications resulting in better treatment outcomes (Kou et al 2018). By enclosing drugs in nanoparticles, they are shielded from degradation in the blood and stay in circulation longer allowing for a release at the tumor site. This prolonged presence boosts drug levels within cancer cells while reducing harm to other parts of the body.

Targeted approaches

Nanoparticles can be designed with targeted strategies to increase their accuracy in reaching cancer cells. By attaching molecules that recognize tumor related receptors or antigens to nanoparticles, they can be precisely delivered to tissues. This targeted method helps concentrate chemotherapy drugs within tumors improving their effectiveness while minimizing harm to cells.

Controlled release mechanisms

Some nanomaterial-based drug delivery systems incorporate response triggering mechanisms that control drug release based on signals from the tumor environment (Abetz 2020). For such occasions, nanoparticles sensitive to pH levels release drugs in tumor areas where solid tumors thrive due to pH levels. This controlled release method enhances drug absorption by cancer cells while reducing exposure making treatments more effective and safer.

Combination treatment options

Nanoparticles provide a platform for delivering combination therapies, in cancer care. By embedding medications or treatments, within a nanoparticle system, a synergistic effect can be achieved, which helps in overcoming drug resistance mechanisms and enhancing the death of tumor cells. Using nanomaterials-based drug delivery systems to deliver combination therapies can improve treatment results thereby reducing the development of resistance over time (Barenholz 2012).

Integration of imaging and therapeutics

Certain nanomaterials can serve functions by combining imaging agents and treatments within the same nanoparticle platform. This allows for tumor imaging and targeted drug delivery aiding in treatment plans and real time monitoring of how well the treatments are working. Nanoparticles with imaging capabilities, such as quantum dots or iron oxide nanoparticles enable the identification of tumors and evaluation of treatment effectiveness (Locatelli et al. 2015).

Future paths and challenges

Research on nanomaterials-based drug delivery for cancer therapy is focused on refining nanoparticle design enhancing drug loading capacities and improving targeting specificity. Obstacles like ensuring biocompatibility establishing long term safety profiles and scaling up manufacturing processes are actively being explored. Furthermore, evaluating aspects and translating nanotechnology-based cancer therapies into practice requires a thorough assessment. In summary, utilizing the concerned drug delivery systems offers an approach, to enhancing cancer treatment outcomes by improving drug stability targeting specificity, and effectiveness while minimizing overall side effects. The ongoing progress, in nanotechnology shows potential, for improving precise cancer treatment in the coming years (Luiz et al. 2022).

Alzheimer’s

In the case of Alzheimer’s disease, a disorder, delivering drugs effectively presents unique challenges due to the blood–brain barrier restrictions. However promising strategies such as ultrasound- and nanotechnology-based carriers have shown progress in overcoming this hurdle by successfully delivering drugs across the blood–brain barrier. The use of ultrasound has shown promise in opening the barrier, which allows drugs to pass through. To further enhance drug delivery, to the brain nanocarriers are utilized to protect the drugs and improve their ability to target areas (Causio et al. 2023). These advancements provide hope for slowing down disease progression and enhancing function ultimately improving the quality of life for individuals affected by Alzheimer’s. Patients with Alzheimer’s can maintain their independence for a period, preserving memories and relationships with loved ones. Cardiovascular diseases such as artery disease and heart failure are causes of global mortality. The treatment of these conditions often requires controlled and prolonged drug delivery to prevent complications and promote healing. A notable example is the use of drug eluting stents in cardiovascular disease treatment. These stents are coated with drugs that are released gradually over time (Mura and Couvreur 2012). By inhibiting cell proliferation and inflammation at the site of the stent these drugs prevent artery re narrowing thereby reducing the risk of heart attacks. This advancement has significantly improved recovery, minimizing interventions needed and enabling individuals to resume their daily activities with fewer limitations.

Improving entry via the blood–brain barrier

Tailored nanoparticles for Alzheimer’s treatment can cross the blood–brain barrier, allowing drugs to reach specific parts of the brain. By modifying nanoparticle surfaces and adding targeting components, these particles are capable of communicating with brain cells thus providing access to the nervous system (Allen and Cullis 2013).

Precise drug distribution

Nanoscale carriers can enclose Alzheimer’s drugs and gradually release them into the brain. This regulated release guarantees that medication levels are maintained at specific sites while lowering exposure throughout the body, hence reducing potential negative effects. Such focused administration improves therapeutic results thereby reducing the likelihood of consequences on neural tissues.

Protecting brain health

Engineered nanoparticles carrying chemicals or antioxidants serve an important function in preventing neurodegeneration and neuronal damage caused by Alzheimer’s disease. Nanoparticles function by capturing radicals, reducing oxidative stress, and promoting brain cell survival, potentially delaying disease development and maintaining cognitive capacities.

The focus on amyloid plaques

Nanotechnology methods for Alzheimer’s disease can directly target amyloid plaques, which are prevalent in the brains of those affected. These plaques can be removed utilizing nanoparticles containing amyloid-targeting chemicals or peptides.

Detecting nano-sensors

Beyond delivering medication nanotechnology provides tools like nano sensors for detection and monitoring of Alzheimer's disease biomarkers. Nanoparticle-based biosensors are capable of identifying amyloid beta peptides or tau protein accumulations in fluids like fluid or blood samples allowing for early intervention and personalized treatment plans (Zhao et al. 2022).

Prospects and obstacles

Ongoing research in nanotechnology for Alzheimer’s disease is focused on overcoming challenges such as ensuring compatibility with living tissues long term safety considerations and the ability to scale up manufacturing processes (Shahbazi et al. 2012). Progress in designing nanomaterials, developing targeted delivery methods and creating nanosystems hold the potential for enhancing Alzheimer’s disease management techniques and improving patients’ quality of life. Utilizing nanotechnology-based drug delivery systems presents solutions for treating Alzheimer’s disease by enhancing penetration, through the blood brain barrier facilitating localized drug administration by targeting amyloid plaques, and offering diagnostic capabilities. These new developments create opportunities, for tailored treatments that could potentially slow the advancement of disease maintenance abilities and improve the results for patients, in managing Alzheimer's disease.

Human immunodeficiency viruses (HIV)

Managing HIV, a retrovirus that weakens the immune system poses a global health challenge. Effective HIV drug delivery plays a role, in addressing this chronic condition. Advancements, in drug formulations like injectables and implants have extended the time between doses making it easier for patients to follow their medication plans. This not only improves their well-being but also slows down the progression of the disease (Aureliano et al. 2023). It gives patients a sense of control over their health. This empowers them to manage their condition resulting in better treatment outcomes and a higher quality of life. When it comes to managing pain, it can greatly impact one's activities and enjoyment of life. However advanced drug delivery systems have revolutionized pain management by offering targeted relief. The examples include pumps for drug delivery implants placed in the spine. The patches are applied on the skin which helps in the release of pain medication while reducing the need for oral dosing and minimizing side effects (Xiong et al. 2023). As a result, patients can experience lasting relief that enhances function mental well-being and overall satisfaction with their pain management routine.

The field of drug delivery has emerged as a game changer, across disciplines by significantly improving the lives of patients grappling with different ailments. Through a humanized approach, to drug delivery, healthcare professionals, researchers, and patients collaborate to develop therapies thereby maximizing the effectiveness of treatments. Additionally, it also minimizes any negative impacts, allowing patients to lead more fulfilling and healthier lives. The continuous progress in drug delivery holds promise for a healthier future for humanity. As researchers and medical experts further explore and refine drug delivery techniques we can expect breakthroughs in the treatment of various diseases. This will create a world where individuals can fully enjoy their lives without being limited by illness. By combining science, compassion, and innovation we can establish a world where every patient receives the care empowering them to face diseases with hope, bravery, and dignity.

Innovative drug formulations

The progress made in drug formulations for treating HIV, like extended release injectables and implants, has transformed how medications are taken (Abetz 2020). These new formulations extend the time between doses making it simpler for patients to stick to their treatment plans. By reducing how medication needs to be taken these fresh approaches not only boost patient convenience but also aid in improving treatment adherence and disease management.

Empowering individuals

The use of extended-release drug delivery systems in managing HIV empowers individuals by giving them control over their health. With dosing requirements, individuals can better handle their condition leading to treatment results and a higher quality of life. This empowerment encourages involvement from patients in managing HIV adding to an overall sense of well-being and success in managing the disease.

Managing pain

It is crucial in HIV care due to symptoms or complications related to pain that patients may experience. Advanced drug delivery systems like pumps for delivering drugs, implants in areas close to pain receptors, and other materials like transdermal patches offer relief for pain linked with HIV or its treatments. These methods release pain medication directly to affected areas in a controlled manner reducing the necessity, for dosing and minimizing widespread side effects.

Improved functionality and quality of life

Utilizing techniques, in pain management through drug delivery methods not only eases discomfort but also enhances the patient’s overall ability to function and emotional welfare. By delivering lasting pain relief and reducing the effects of medications these strategies allow individuals to participate in daily tasks experience a higher standard of living and feel content with their pain management routine.

Final prospects

Innovative drug delivery systems play a role in the treatment of HIV by providing sustained release formulations that empower patients and deliver pain relief. These developments boost compliance with treatment and disease management. Also enhances patient well-being, functionality, and overall satisfaction with their healthcare journey, in controlling HIV.

Nanomaterials-based delivery cargo

Nanotechnology has advanced rapidly over the past several decades, significantly impacting the medical field, particularly in the area of drug delivery systems. (Akhter et al. 2018). The transport of drug compounds into the human body is called drug delivery (Table 2). A variety of technologies are used to safely introduce therapeutic compounds into the body to achieve the desired therapeutic effect (Edgar and Wang 2017). The most used methods of drug delivery are oral and injection. Medicines are expected to circulate throughout the body and affect dysfunctional cells along with healthy organs. The effect of the drug is limited in our body due to its ability to reach the target site. Only a small number of drugs could achieve its target (Singh 2011). To overcome limitations such as low therapeutic indices, poor water solubility, and limited targeting, nanoparticles are used as carriers in drug delivery systems (Edgar and Wang 2017). In medical science, cargo delivery is one of the advanced approaches to drug delivery (Manshadi et al. 2018). Cargo acts as a carrier in the drug delivery system. It carries therapeutic agents like drug molecules, chemotherapeutics, antibodies, vaccines, proteins, peptides, aptamer, DNA, etc. from the site of application to the target point (Akhter et al. 2018). In 1911, cargo was injected into individual cells and it was the first case of intercellular cargo delivery (Fig. 3). This method has so many biological importances such as gene editing and biological therapy (Tay and Melosh 2019).

Table 2.

Tabular representation of different organic and inorganic delivery cargo system, their production process and application area

Sl No	Cargo	Production method	Application areas	References
1	Polymeric nanoparticles (nanospheres)	Solvent evaporation, Emulsification/ solvent diffusion, nanoprecipitation, reverse salting out	Drug delivery, theragnostic, bioimaging, anti-glioma activity, anti-inflammatory activity, diabetic retinopathy	Guterres et al. (2007); Zielinska et al. (2020)
2	Polymeric nanoparticles (nano capsules)	Nanoprecipitation	Anti-fungal activity, anticancer, undefined oral delivery, anti-bacterial activity, anti-microbial activity, anti-oxidant activity	Bohrey et al. (2016)
3	Inorganic nanoparticles Gold nanoparticle Silver nanoparticle	Chemical method: template method, Brust method, Martin method, two phase method, seed-mediated method, hot-in junction technique, Perrault method Physical method: sonolysis, y-irradiation method Green method: green biosynthesis method, sunlight irradiation method, sunlight irradiation method, new green chemistry method Chemical method: microemulsion technology, UV initiated photoreduction, photo-induced reduction, electro chemical method, Electro chemical synthetic method, pyrolysis method, pyrolysis Physical method: physical vapor condensation, Arc-discharged method Bio-based: Evaporation method from bacteria, fungi, yeast, plants	Osteoinductive effect, antibacterial activity, antifungal activity, antiviral activity, and anti-inflammatory activity	Pandey and Dahiya (2016)
4	Liposome	Conventional Technology, DepoFoam Technology, Stealth Liposome Technology, Non-PEGylated Liposome Technology, Detergent Removal Technology	Cancer Therapy, Fungal Infection, Analgesics, Viral Vaccines, Photodynamic Therapy
5	Carbon Dot	Synthesis Method- Microwaving, Refluxing, Hydrothermal method, Ultrasonication, Solvothermal in Ethylene Glycol Solvent, Sonochemical Method, Calcination, Hydrothermal Carbonization, Chemical Oxidation, Pyrolysis, Ultrasonic Wet Chemical Oxidation, Sand Bath Assisted method	Sensor for Iodide and Hg2+, Cell Imaging and Sensing, Detection of Picric Acid, Fluorescent Probes, Multicolour Bioimaging, Detection for Fe3+, Bio-imaging of Breast Cancer Bcap-37 Cell, Nanophotonic, Theranostic application, Druf carrier for acetaminophen, Adsorbent for Naphthalene, Photocatalyst for degradation of Naphthol Blue-black Azo Dye	Kurian and Paul (2021)
6	Micelle	Simple dissolution, dialysis, oil in water emulsion, solvent evaporation, lyophilization, freeze drying	Drug carrier, imaging contrast agents, chemotherapeutic agents, carrier for gene delivery	Bilia et al. (2016)

Fig. 3.

Representation of various types of nano-sized cargo involved in drug delivery. Micelle, dendrimer, liposome, nano capsule, etc. are organic based and PLGA, PEG, etc. are synthetic based cargo

Polymeric nanoparticles

Polymeric nanoparticles (NPs) have gathered widespread acknowledgment over the last decade for their extremely small size and the properties that come with it (Cano et al. 2020). Polymeric NPs have a few important advantages as drug carriers. Their potential includes controlled release, improved bioavailability, protection of the drug against any chemical interference, and a better therapeutic index (Owens and Peppas 2006). The word ‘nanoparticle’ includes two groups of NPs, which differ from each other based on their morphology. These are called ‘nanocapsules’ and ‘nanospheres’. Nanospheres comprise a continuous polymeric network that encapsulates the drug and the drug can get adsorbed to the outer surface of the NP. SEM and TEM were used for performing morphological analysis of these NPs, along with various other cryofracture techniques (Bohrey et al. 2016). The surface morphology of these NPs is studied using another technique known as AFM. AFM is a high-resolution, three-dimensional analytical device that is capable of resolving characteristics of the surface at the atomic level on the nanometric scale (Carbone et al. 2018). The chemical composition of NP is generally done via a single-particle elemental analysis method or an ensemble. Atomic absorption spectroscopy is one of the most widely practiced ensemble techniques, based on atomic absorption and ground state electron excitation principle (Mourdikoudis et al. 2018). Similarly, time of flight-MS (TOF–MS) is a technique used for analyzing and determining the chemical composition of a single particle using a time-of-flight mass analyzer (Tay and Melosh 2019). Polymeric NPs have had a significant impact on medicine, but their application in the clinical field requires to be critically controlled as its components may have a risk of potential toxicity. But nowadays these NPs and biodegradable and can be easily excreted out via normal metabolic pathways (Lima et al. 2020). All the components of the formulation have to be screened for inherent toxicity (Calzoni et al. 2019).

Advantage. Polymetric nanoparticles have a wide range of size, shape, and composition possibilities, making them ideal for a variety of applications including medication administration, imaging, and diagnostics. Many polymers employed in nanoparticle manufacturing are biocompatible, which reduces the possibility of immunological responses or toxicity when utilized in biological systems. The porous nature of certain polymeric nanoparticles allows for the regulated release of encapsulated medicines, which improves therapeutic effectiveness.

Disadvantage. The production of polymeric nanoparticles can produce changes in size, shape, and characteristics from batch to batch, compromising reproducibility and quality control. Some polymeric nanoparticles may have limits in terms of drug loading capacity, reducing their effectiveness in drug delivery applications, which might be detected and removed by the immune system.

Inorganic nanoparticles

Inorganic nanoparticles have been a source of fascination for scientists all around the globe for over a century. Inorganic NPs have made their way in to the medical industry and now are an integral and inevitable part of it. They have widespread application in the field of biotechnology due to their flexibility to be modified with functional groups as per requirement. This feature enables them to conjugate themselves with the proteins, molecules, and drugs of interest. Metallic inorganic nanoparticles like iron (II, III) oxide, gold NPs, silver NPs, etc. are used for imaging modalities because of their contrasting nature (Pandey and Dahiya 2016). Gold Nanoparticles (GNPs) are from 2 to100 nm in size. The most efficient cellular uptake is shown by GNPs ranging from 20 to 50 nm in size. GNPs in the range of 40–50 nm have been reported to show specific toxicity (El-Sayed et al. 2006). These particles function by diffusing to the tumors and then recovering their cells (Jadzinsky et al. 2007). The distinct characteristics (physical and chemical) Of GNPs accentuate their efficiency in drug delivery and biocompatibility (Khan et al. 2014). Various types of GNPs include gold nanocages, gold nanospheres, gold nanorods, and gold nanoshells (Han et al. 2006). Silver Nanoparticles (AgNPs) are used for Cancer Therapy and have been reported to show cell-specific cytotoxicity against Human Cancer cells like Breast Cancer cells (Han et al. 2006). AgNPs show optical properties (Pulit et al. 2013) hence can be used as biosensor materials (Alahmad 2014). They also show osteoinductive effect, antibacterial, antifungal, antiviral, and anti-inflammatory effects (Qu et al. 2014). Certain nanoparticles, such as dendritic mesoporous silica nanoparticles (MSND), can enhance drug delivery efficiency by improving cellular uptake and mucus retention. Hence, it increases bioavailability and efficacy in related disease treatments. Morphology of mesoporous silica nanoparticles can enhance drug delivery in IBD treatment. MSNDs can reduce inflammation and improve therapeutic efficacy in colitis. (Li et al. 2024). Inorganic nanoparticles can also be used as scaffolds for biorthogonal catalysts. They can promote bioavailability and efficiency in disease treatments by providing a stable and target-specific delivery system. Inorganic nanoparticles offer enhanced physicochemical properties that enable synergistic combinations with anti-microbial peptides and antibiotics. This in turn improves therapeutic outcomes against infectious diseases (Tsikourkitoudi et al. 2022).

Nanospectra Biosciences has designed and developed a gold nanoparticle called AuroLase. These were polyethylene glycol (PEG) coated silica-gold nanoshells. They coated the nanoparticles to provide overall particle stability. Schwartz et al. 2009 demonstrated the use of AuroLase for thermal ablation treatment of brain cancer tumors and Stern et al. 2008 showed the use of AuroLase for thermal ablation treatment of solid tumors in prostate cancer via systemic injection of the nanoparticles. Another such nanoparticle was designed by Sebacia Inc. called Sebashells. These silica–gold nanoparticles were 150 nm in length and also coated with PEG. Paithankar et al. showed the use of these nanoparticles to treat acne by focal thermolysis of overactive sebaceous glands present on the skin.

Advantage. Inorganic nanoparticles have high chemical and physical stability that enhances their performance under different conditions. They also possess unique properties like electrical, magnetic, and optical properties which are very beneficial for drug delivery, imaging contrast enhancement, and therapeutics. They are suitable for long-term applications because of their durability. These nanoparticles provided localized tumor treatment, limiting the damage caused to healthy tissues. The advantage of using such nanoparticles is that they avoid several systemic side effects associated with traditional therapies like chemotherapy.

Disadvantage. Some inorganic nanoparticles like heavy metal-based nanoparticles may possess toxicity because of their composition. They have limited use in biological applications as not all inorganic nanoparticles are biocompatible. Their synthesis is a very complex chemical process. These nanoparticles also pose some limitations. Tuning, surface optimization, and physical properties are some concerns.

Liposomes

Liposomes generally are in the range of 60 nm comprising around 60,000 phospholipid molecules. These have the highly advantageous feature of being able to be modified according to the requirement of chain lengths, head groups, or chain saturation. Cationic lipids have a net positive charge and hence, enhance electrostatic interactions with DNA and cell membrane, which are negatively charged. Anionic lipids have a net negative charge on them and they share the same charge as the cell membrane or DNA. Zwitter ionic lipids possess both positive and negative charges, hence there is no net charge on its surface (Qu et al. 2014). A liposome is made up of a phospholipid, cholesterol, and a charging agent for a specific purpose or as an anti-agglomerative (Haghiralsadat et al. 2017). The governing factors of the process of drug loading include the polymorphic states of lipids, the solubility of the drug in melted lipids and the physicochemical structure of the solid lipid matrix (Haghiralsadat et al. 2017). According to Thode et al. 2000, with increase in the effective area of particles, there is a rise in drug release (Thode et al. 2000).

Advantage. Liposomes are usually biocompatible because they are made from natural phospholipids which make them well-tolerated in biological systems, reducing the risk of adverse reactions. They enable targeted drug delivery to specific tissues and cells because they can encapsulate both hydrophobic and hydrophilic drugs. They are highly versatile as they can be modified with targeting ligands or surface functionalized to improve stability, circulation time, and targeting efficiency.

Disadvantage. Liposomes usually have stability issues like leakage or degradation during storage or circulation which affects their efficacy and shelf life. They have limitations in drug loading capacity, especially for hydrophobic drugs. They suffer from batch-to-batch variability due to their manufacturing process.

Carbon dot

Carbon dots are characterized as core–shell nanocomposites. They comprise a carbon core encased with surface passivation, featuring an array of functional groups (for example: hydroxyl groups, carboxyl groups, amino groups, etc.). The presence of these functional groups makes them hydrophilic and aids in passivation and functionalization (Thode et al. 2000). These NPs are up-and-coming for biomedical and clinical sciences, notably in biosensors, bioimaging, bioanalytical assay, and diagnosis (Thode et al. 2000). Post-synthetic alterations of carbon dots play a critical role, as the incorporation of functional moieties such as amines, and carboxyl groups can induce diverse imperfections on the carbon dot exterior. These imperfections function as traps for excitation energy, resulting in notable fluctuations in fluorescence emissions. The functionalization of the surface with these groups not only originates fluorescence-inducing surface flaws but also furnishes potential reactive sites for tailored modification procedures. By employing these reactive moieties, an array of distinct organic, polymeric, inorganic, and biomaterials can be attached to carbon dot surfaces through covalent and hydrogen bonding, as well as electrostatic interactions. This attachment serves as a foundation for specific applications such as sensing and targeted drug delivery, among others (Liu et al. 2016). Carbon and graphene quantum dots possess remarkable qualities that make them highly suitable for contemporary electrochemical biosensing applications. Their exceptional solubility in diverse solvents, inherent low toxicity, impressive electronic properties, robust chemical stability, substantial specific surface area, and the presence of numerous edge sites for functionalization contribute to their appeal. Additionally, these quantum dots exhibit significant biocompatibility, cost-effectiveness, versatility, and the potential for substantial surface modifications, including the incorporation of nanostructured materials. These attributes enable the utilization of quantum dots as signal markers or modifiers for electrode surfaces, thereby facilitating the development of electrochemical biosensing methodologies (Liu et al. 2016). Generally, carbon and graphene quantum dots, despite their varying structures, exhibit largely analogous optical attributes. These attributes encompass optical fluorescence, absorption, chemiluminescence, electrochemiluminescence, phosphorescence, up-conversion photoluminescence, and the property of photo-induced electron transfer. These materials have garnered significant interest owing to their exceptional ability to fine-tune optical properties, cost-effectiveness, straightforward manufacturing processes, and minimal toxicity. These factors collectively position carbon and graphene quantum dots as optimal contenders for employment in optical sensor applications (Liu et al. 2016).

Carbon dot nanoparticles (CDs) have demonstrated considerable potential in improving the bioavailability and efficacy of pharmaceutical agents in various treatments. CDs, characterized by their biocompatibility, minute particle size (< 10 nm), and distinct physicochemical attributes, function effectively as excellent conveyors of therapeutic drugs (Bhavikatti et al. 2024; Kong et al. 2024). The application of CDs for the delivery of anti-inflammatory, antibacterial, and anticancer medications has exhibited heightened drug potency, regulated release, enhanced specificity, and diminished systemic adverse effects in comparison to unbound drugs (Qi et al. 2023). Furthermore, CDs present adjustable photoluminescent and fluorescent characteristics that facilitate real-time tracking of drug distribution, thus rendering them invaluable assets in drug conveyance platforms for accurate and efficient disease management.

Several carbon dot nanoparticles have been studied by research groups for the treatment of various types of cancer cells. Li et al. 2016 studied the effect of carbon dots on pediatric brain tumor cells. They used Doxorubicin-loaded carbon dots for their clinical study and its effect on pediatric brain tumor cells. Doxorubicin is generally prescribed by several medical institutions for the treatment of sarcomas, leukemia, and lymphomas (Tacar et al. 2013). Many other independent researchers have also seen promising results in the treatment of breast cancers and brain tumors using Doxorubicin-loaded carbon dots (Li et al. 2016; Woods et al. 1994). Similarly, Gemcitabine-loaded carbon-based nanoparticles have been demonstrated by several researchers to show positive results in preventing metastasis and inhibiting tumor growth of some cancer types (Yang et al. 2009, 2011; Singh et al. 2013).

Advantage. Carbon dots are generally biocompatible and exhibit low cytotoxicity as they are made from carbon sources like carbon nanotubes or graphene oxides which makes them suitable for biomedical applications. They possess unique optical properties that help in bioimaging, sensing, and diagnostics. They are eco-friendly as compared to other nanoparticles (Dey et al. 2013).

Disadvantage. Carbon dots produced from different carbon sources or under different circumstances might have varying features such as size, fluorescence intensity, and surface chemistry, making standardization challenging.

Image-guided nanomaterials

The application of both hard and soft nanoparticles in therapeutic endeavors, collectively termed nanomedicine, holds substantial promise in the ongoing fight against cancer. This field is witnessing significant research outburst that are driving the innovation of novel methods for drug delivery and imaging techniques aimed at addressing cancer. Organic-based soft nanoparticles present a robust foundation for effectively incorporating and delivering active agents in the realm of image-guided surgery (IGS). This disparity may be attributed to the inherent characteristics of hard-core nanoparticles, (for example: magnetism and luminescence) and their prowess to function as contrasting agents. These attributes are not inherently present in the soft nanoparticles. Consequently, to imbue soft nanoparticles with imaging capabilities, the integration of the specific components like fluorescent dyes, becomes necessary. The pioneering instance of a soft nanoparticle system in the domain of image-guided surgery (IGS) was introduced by Tanaka et al. in 2006. In this particular study, HSA was harnessed to fabricate soft nanoparticles, subsequently linked with the fluorophore CW800 and the ICG dye. A comparative analysis with QDs underscored the enhanced biocompatibility of the HSA-based system, although luminescence and stability characteristics stayed more favorable for QDs. Given this distinction, the details of this study will be further elaborated upon in the subsequent section discussing nanosystems centered on hard-core nanoparticles. Over the recent years, there has been a continuous increase in reported cases where Image-Guided Surgery (IGS) has been enhanced through the incorporation of Hard-core nanoparticles. A range of tumor types can gain significant advantages from intraoperative visualization. However, up until now, the literature has predominantly focused on a limited set of targets. One such target is malignant melanoma treatment, a context in which the identification of lymph node metastases holds paramount importance for prognosis determination and subsequent therapeutic strategies. While surgical resection is generally successful in treating this form of cancer, accurately determining the stage of melanoma through the sentinel lymph nodes remains a complex task, primarily due to the impact of the inflammatory conditions and the current lack of dedicated intraoperative probes (Locatelli et al. 2015).

The nanoparticles provide precise targeting and image guidance, as evidenced in the management of lung cancer utilizing nanotheranostic H-dots loaded with gefitinib and genistein. By offering accurate guidance for tumor resection and delivering anti-cancer drugs to targeted sites, these nanoparticles facilitate a synergistic approach to therapy while mitigating adverse reactions and drug resistance (Yin et al. 2022). Furthermore, the morphology and composition of nanoparticles have a significant influence on their therapeutic efficiency, with specific shapes such as flat scrolls and oblates demonstrating superior efficacy in suppressing lung tumor growth and inhibiting metastasis (Liu et al. 2021).

Lamichhane et al., 2018 demonstrated the use of image-guided nanoparticles for the treatment of breast cancer and leukemia. They showcased the usage of Grb-2 image-guided liposomal nanoparticles for clinical trials. Grb-2 acts by inhibiting the proliferation of tumor cells because of the presence of antisense oligodeoxynucleotide (Tari et al. 2007). In 2018, Lamichhane and colleagues also discussed the use of LEM-ETU liposomal-image-guided nanoparticles for the treatment of several types of cancers such as liver, stomach, and ovarian cancers (Wicki et al. 2015; Ahmad et al. 2005).

Advantage. Image-guided nanomaterials can give real-time image feedback during medical treatments, allowing for accurate identification and targeting of sick tissues or cells. Some image-guided nanomaterials combine diagnostic and therapeutic functionalities, enabling simultaneous imaging and therapy, and potentially improving treatment results and patient care. Image-guided nanomaterials can be loaded with targeting ligands or imaging agents to preferentially accumulate in target tissues, reducing off-target effects and increasing therapeutic effectiveness (Phillips et al. 2014).

Disadvantage. The synthesis, characterization, and clinical translation of image-guided nanomaterials can be expensive, restricting their availability, and use in clinical practice, particularly in resource-constrained areas. Image-guided nanomaterials may raise safety concerns related to potential toxicity, immunogenicity, or long-term effects, necessitating comprehensive risk assessment and mitigation strategies. The creation and optimization of image-guided nanomaterials need multidisciplinary collaboration among scientists, engineers, and doctors, which may be difficult and time-consuming.

Micelle

In a diluted state, polymers exist as individual dispersed units within a medium. As the concentration reaches a certain threshold, these polymers tend to organize themselves into an ordered structure, a phenomenon referred to as the “critical micelle concentration” (CMC) (Wu et al. 2020) This critical point can be determined through surface tension measurements, as the surface tension experiences a pronounced shift with changes in molecule concentration (Kwilas et al. 2015). Consequently, the concentration at which the surface tension ceases to change is designated as the CMC (Kwilas et al. 2015). The outcomes stemming from the autonomous assembly of amphiphilic polymers or their spontaneous aggregation are termed “micelles” and “vesicles.” These micelles and vesicles hold significant importance in a range of applications (Bilia et al. 2016). Micelles constitute monolayers formed through the self-assembly of polymers, whereas vesicles manifest as bilayers of self-assembled polymers (Brinkhuis et al. 2011). While a wealth of information exists about vesicles in various reports and reviews, this discussion narrows its focus to polymeric micelles (Zhu et al. 2017). The formation of micelles is notably influenced by the CMC, which assumes a pivotal role in the process (Sun et al. 2021).

Matsumura, (2008) discussed the use of micellar nanoparticles loaded with paclitaxel for the treatment of various cancers like ovarian, breast, and lung cancers. Matsumura and Kataoka, 2009 demonstrated the use of Cisplatin (cis-dichlorodiammineplatinum [II]) loaded micellar nanoparticles for the treatment of some cancer types which include gastrointestinal, lung, and genitourinary cancers.

Advantages. Micellar nanoparticles present numerous advantages in the field of drug delivery, as they possess the capacity to encase a wide array of therapeutic cargo, traverse biological obstacles to target specific locations within the organism, and efficiently discharge cargo in response to internal or external stimuli (Maximilian et al., 2024). In addition, intelligent nanoparticles, including micelle-based nanoparticles that respond to stimuli, have the potential to amplify drug effectiveness, diminish toxicity, and surmount drug resistance by employing induced drug release mechanisms (Mahboudi et al. 204).

Disadvantages. Micellar nanoparticles possess some issues regarding their stability, reproducibility, clinical safety, and biocompatibility (Maboudi et al. 2024). Moreover, the disparity between advancements in creating innovative therapeutic strategies utilizing nanotechnology and their integration into clinical settings poses a significant challenge that must be tackled to augment the efficacy of micellar nanoparticles in drug delivery for illnesses like breast cancer (Yazdan et al. 2024).

Nanofiber

These are the ultimate fibers with a diameter of less than 1000 nm. Due to their special characteristics and nanoscale size, these fibers are of great interest to many scientific fields and industrial. Polymers, carbon, metals, ceramics, and composites are just a few of the materials that can be used to create nanofibers; each has unique qualities that make it suited for a particular use. Numerous techniques, including electrospinning, melt-blowing, and template synthesis, may be used to create nanofibers, each of which has an impact on the ultimate structure and characteristics of the resulting materials. Due to its excellent mechanical qualities and huge specific area, big aspect ratio, and nanoscale size, nanofiber is employed extensively in various fields such as air filters, medication delivery, and batteries (Chen et al. 2022). Nanofibers are utilized to replace human tissues and organs that are physically or physiologically defective since they are biocompatible and biodegradable (Venugopal and Ramakrishna 2005). As a result of their enormous surface area and porosity, nanofibers are utilized in a variety of applications, including filter media, adsorption layers in protective clothing, and so on (Subbiah et al. 2005). The material and production technique used to create nanofibers affect their structure and are classified into several types according to their structure. Some of them are polymeric nanofiber, ceramic nanofiber, and carbon nanofiber.

Typical fabrication methods include the following:

Electrospinning. This method is frequently employed to create ceramic nanofibers. In this method, a solution containing ceramic precursors is electrospun to create a fine jet that solidifies into nanofibers when collected on a substrate. Heat treatment can transform the resultant nanofibers into ceramic form.

Template-assisted synthesis. In this technique, porous templates with distinct nanostructures are used such as anodic aluminum oxide (AAO) templates. Once the ceramic precursors have been inserted into the template’s pores and transformed into ceramics, the template is removed, leaving the ceramic nanofibers behind.

Chemical vapor deposition. CVD is a different method for creating ceramic nanofibers. In this method, ceramic precursors are thermally broken down in a gas phase, and the resulting ceramic nanofibers are then deposited on a substrate.

Sol–gel processing. Sol–gel is a solution-based method for creating ceramic fibers by electrospinning or spin-coating a ceramic gel created by the hydrolysis and condensation of a precursor solution. Depending on the particular ceramic material, ceramic nanofibers have a variety of special qualities, including increased surface area, improved mechanical strength, good thermal stability, and electrical characteristics.

Ceramic nanofibers

Ceramic nanofibers offer great potential for a wide range of applications because of their unique properties. These are used in the electronics sector because of their dielectric and thermal stability. Ceramic nanofibers are generally considered non-toxic and biocompatible, promoting cell growth without significant cytotoxic effects. They exhibit low toxicity in human pulmonary cells and are biodegradable, which reduces long-term risks associated with accumulation in biological systems, however, oxidative stress and inflammation can occur due to free radical production, necessitating careful evaluation of their long-term effects. These nanofibers are considered safe for drug delivery applications due to their excellent biocompatibility and ability to promote tissue regeneration. They can facilitate the controlled release of therapeutic agents and are easily sterilizable, making them suitable for various medical applications. They are utilized as fillers in polymer composites for printed circuit boards and as dielectric materials in capacitors. Certain ceramic nanofibers, such as bioactive glass nanofibers that promote cell attachment and growth, have shown promise in the fields of tissue engineering and regenerative medicine. (Wen et al. 2020). Manufacturing ceramic nanofibers typically involves techniques such as electrospinning and centrifugal spinning, which allow for continuous production and high productivity. These methods can produce nanofibers with complex morphologies and are being optimized for cost-effectiveness and efficiency. Ceramic nanofibers are fibers that are only a few nano meters long and have a high aspect ratio, which gives them special features. These nanofibers generally have sizes between a few and several hundred nano meters. These are employed in a range of sectors, including electronics, aerospace, catalysis, energy storage, and medical applications, because of their exceptional qualities and capacities (Sahoo et al. 2022). Ceramic nanofibers generally exhibit good storage stability, with ceramic nanofibers being particularly resistant to degradation due to their inorganic nature. Various techniques can be used to create ceramic nanofibers, depending on the particular ceramic material and desired qualities.

In a clinical trial, it was shown that the use of ceramic nanofibers composed of calcium phosphate for bone regeneration in patients with critical-sized bone defects. The study involved 30 patients who received implants made from electrospun calcium phosphate nanofibers. The primary endpoints were bone healing and integration assessed through radiographic imaging and histological analysis over 12 months. The results indicated that the ceramic nanofibers promoted significant bone regeneration, with a 75% success rate in achieving complete integration into the surrounding bone tissue. Histological evaluations showed new bone formation and vascularization around the nanofiber scaffolds, demonstrating their effectiveness as a biomaterial for bone repair. In another study, focus was given to the application of SiO₂–CaO–Er₂O₃ flexible ceramic nanofibers in wound healing. This study enrolled 20 patients with chronic wounds, who were treated with a nanofiber mat applied directly to the wound site. The primary outcome measures included wound closure rate and pain levels reported by patients over 6 weeks. The findings revealed that patients treated with the ceramic nanofiber mat exhibited a significantly faster wound closure rate compared to the control group receiving standard care (mean closure time of 14 days vs. 21 days, p < 0.05). Additionally, patients reported lower pain levels associated with the nanofiber treatment, indicating enhanced comfort during the healing process (Kizildag 2021).

Carbon nanofibers (CNFs)

These are a special type of carbon nanomaterial that share carbon nanofibers’ (CNFs’) conductivity and stability. Carbon nanofibers, particularly carbon nanotubes, present higher toxicity risks. They can induce inflammatory responses and oxidative stress, leading to potential cytotoxic effects. Their reactivity and ability to penetrate biological membranes raise concerns about their safety in biomedical applications, requiring extensive research to mitigate these risks. Due to their relative chemical inertness in most electrolyte solutions, cheap cost, and very large potential windows in aqueous settings, carbon compounds are excellent for the fabrication of electrodes used in electroanalytical chemistry. The safety of carbon nanofibers for drug delivery is questionable due to their potential cytotoxicity. While they can enhance drug delivery efficiency, their adverse biological effects need to be carefully evaluated before clinical use. Carbon nanofibers are primarily produced through chemical vapor deposition (CVD) and electrospinning. While CVD yields high-quality fibers, it can be expensive and less scalable. Electrospinning offers a more scalable solution, enabling the production of aligned nanofibers tailored for specific applications. In addition to glassy carbon, amorphous powders, nanotubes, carbon fiber, graphite, and diamond, carbon materials can also have a range of microstructures. Carbon nanomaterials, in particular carbon nanofibers and carbon nanotubes, have drawn a lot of attention in electro-analysis and biosensing with the growing growth of nanotechnology in material science (Huang et al. 2018).

Investigation shows the use of carbon nanofiber scaffolds for enhancing bone regeneration in patients with critical-sized bone defects. In this study, 20 patients underwent surgical implantation of carbon nanofiber-based scaffolds into their bone defects. The primary outcomes measured included bone healing, integration, and the formation of new bone tissue assessed through radiographic imaging and histological analysis over a 12-month follow-up period. The results indicated that the carbon nanofiber scaffolds supported significant bone regeneration, with a reported 80% success rate in achieving complete integration into the surrounding bone tissue. Histological evaluations demonstrated new bone formation and vascularization around the scaffolds, confirming their effectiveness as a biomaterial for bone repair. This trial highlighted the potential of carbon nanofibers in promoting osteogenesis and their applicability in bone tissue engineering (Nemati et al. 2019).

Another clinical trial focused on the application of carbon nanofiber-reinforced hydrogels for cartilage regeneration in patients with osteoarthritis. This study enrolled 30 patients who received injections of carbon nanofiber-reinforced hydrogel into their affected joints. The primary endpoints included pain relief, functional improvement, and cartilage regeneration assessed through MRI and patient-reported outcomes over 6 months. The findings revealed that patients treated with the carbon nanofiber-reinforced hydrogel experienced significant improvements in pain relief and joint function compared to the control group receiving standard treatment. MRI assessments indicated enhanced cartilage regeneration in the treated joints, suggesting that the incorporation of carbon nanofibers into hydrogels can improve the mechanical properties and biological performance of the scaffold. This trial demonstrated the potential of carbon nanofibers in enhancing the efficacy of hydrogels for cartilage tissue engineering applications (Pandey et al. 2021).

Polymeric nanofiber

Among nanomaterials, polymeric nanofibers constitute a significant class. The nanofibers have a diameter of less than 100 nm (Özonur et al. 2006). PGA, PLA, and their random copolymer poly(glycolide-co-lactide) are frequently utilized as the building blocks for implant devices including scaffolds and structural fibers. These materials can give excellent efficiency in drug loading in addition to meeting various controlled-release parameters. Polymeric nanofibers generally show lower toxicity, but their safety can vary based on the specific polymer and additives used. While many polymeric nanofibers are biocompatible and suitable for drug delivery, concerns about leaching toxic substances or degradation products must be addressed. Polymeric nanofibers are often used in drug delivery systems due to their good safety profiles and ability to be engineered for specific release profiles. However, the potential for toxic additives requires thorough evaluation to ensure their long-term safety in medical applications. Microspheres, foams, and films with nanostructured biodegradable structures have been produced utilizing several techniques. It has been shown that PLA, PGA, and their copolymers' molecular structure and morphology can have a significant impact on the mechanical qualities and degradation of the finished goods (Venugopal and Ramakrishna 2005). Natural and synthetic polymers are typically used to create polymer nanofibers, which can be synthesized by various techniques, a few of which include template synthesis, direct stretching, wet spinning, solution-blowing spinning, melt-blown, electrostatic spinning, plasma-induced synthesis, self-assembly, centrifugal jet spinning, and pressurized spinning (Duan et al. 2022). The electrospinning technique may be used to prepare both synthetic biocompatible or bio absorbable polymers and natural biomaterials for biomedical applications. A suitable substrate for the treatment of bone abnormalities may be polycaprolactone (PCL), which has mostly been studied for long-term implants for drug release and support for the development of mineralized tissue. By co-polymerizing with PLA, PCL’s mechanical characteristics have been enhanced, making it suitable for orthopedic uses such as the repair of bone deformities. Polymeric nanofibers may face challenges related to moisture absorption and degradation over time, depending on the polymer used. Proper storage conditions are essential to maintain their integrity and functionality in applications. Various studies were performed that evaluated the use of electrospun polycaprolactone (PCL) nanofiber scaffolds for bone regeneration in patients with critical-sized bone defects. 30 patients received PCL nanofiber implants, and after 12 months, 70% showed complete integration of the scaffold with new bone formation confirmed by imaging and histology. This demonstrated the potential of electrospun PCL nanofibers to facilitate bone tissue engineering (Silva et al. 2022).

In another trial, PLGA-based nanofiber scaffolds were used for cartilage regeneration in 25 patients with joint defects. After 6 months, patients receiving the PLGA nanofiber implants exhibited significant cartilage regeneration on MRI and reported reduced pain with improved joint function compared to controls. This highlighted the ability of polymeric nanofiber scaffolds to enhance cartilage repair (Aoki et al. 2020).

Electrospinning

Electrospinning is the most adaptable method for fabricating nanofibers. This technique produces charged threads from polymer melts or solutions as small as a few hundred nanometers in diameter (Teo et al. 2006). The invention of electrospinning happened in the 1930s and evolved from the study of William Gilbert in the earlier seventeenth century, since then it has found various applications in the field of nanotechnology and biomaterials (Mirjalili and Zohoori 2016). Electrospinning has been used to create materials including ceramic, composites, polymer, and metal nanofibers either directly or after further spinning. Electrospinning is different from other fabrication techniques because of its capacity to create different fiber assemblies. This will undoubtedly improve the functionality of goods created from nanofibers and enable adjustments for certain applications. Electrospinning is associated with the use of an electric field to draw a charged polymer solution or melt it into a fine jet that elongates and solidifies into very thin fibers as it travels towards a grounded collector. This process creates nanofibers with a high surface area-to-volume ratio.

Instrumentation

The process of electrospinning involves drawing a charged polymer solution or melting it into a tiny jet that moves in the direction of a grounded collector, elongating and solidifying into very thin fibers. Through this method, high surface area-to-volume ratio nanofibers are produced. (Fig. 4). Parts of electrospinning machinery are discussed below,

Fig. 4.

Process design of nanofiber fabrication using electrospinning mechanism. A Schematic diagram of electrospinning which contains a syringe, polymer solution, voltameter, and collector. B Scanning Electron Microscope (SEM) images of electrospun nanofibers generated from electrospinning process

A high voltage power supply. A liquid droplet is electrified and introduced to the polymer solution to produce a jet, and then the droplet is stretched and elongated to create fiber. The voltage applied is high enough to cause the polymeric solution's surface tension to break, allowing a jet of nanofiber to develop.

A flow controller. The electrospinning was steady with very few invisible droplets on the collector at a modest flow rate of 0.5 mL/hr. But at flow rates of 1 and 1.5 mL/h, they saw an increase in the gravitational force's influence, which led to twisted Taylor cones and more droplets forming.

A spinneret. It is a hypodermic syringe needle. A spinneret is a machine that turns a polymer solution or melts into nanofibers by using a high voltage. It is coupled to a syringe pump, a grounded collector, and a high-voltage (5 to 50 kV) direct current power source. The spinneret may be made of metal or an insulator and may take on several forms, including cylinders that revolve inside solutions and electrospin. Multiple Taylor cones have also been successfully produced using slit and line spinnerets (Haider et al. 2018).

Procedure

Preparation of natural polymer solution

Natural polymer is isolated or extracted from the source material using different techniques like enzymatic digestion or alkaline treatment. The goal of alkaline treatment is to solubilize the target polymer and break down non-polymeric components in the raw natural material. This is frequently used to create cellulose-based polymers from resources like cellulose. In this method, alkaline reagents like sodium hydroxide are commonly used. Enzymatic digestion includes utilizing certain enzymes to separate the desired polymer from the various parts of the raw natural material. This technique is frequently applied to substances like collagen and silk fibroin. An enzyme is selected that targets the material’s non-polymeric components selectively. Protease enzymes, for instance, can be used to extract sericin from silk strands. By combining the natural polymer with an appropriate solvent, you may the polymer solution can be created. The solubility of the polymer determines the solvent to use. For example, acetic acid can be used for chitosan whereas water is frequently utilized for polysaccharides like cellulose. Then to achieve even disintegration of the polymer, gently stirring or sonicating is performed, this also helps to get rid of any undissolved particles, and the solution is filtered.

Setting up the electrospinning apparatus

A safe place should be chosen for the high-voltage power supply. The spinneret is connected to the power supply’s positive terminal and the collector to the negative terminal. The syringe pump is attached to the syringe that contains the polymer solution. The collector remains between the spinneret and an appropriate distance; this spacing is frequently between 10 and 30 cm. Both the diameter of the fiber and its alignment may be affected by the distance chosen for electrospinning.

Initiating electrospinning

The high-voltage power source has to be turned on while adjusting the voltage to the characteristics of the natural polymer. To minimize potential problems like bead production, it is started with a lower voltage and gradually raised. To feed the polymer solution through the spinneret, the syringe pump is started at a predetermined flow rate. The diameter and shape of fibers are influenced by flow rate. The pace at which the polymer solution is delivered from the syringe to the spinneret during the electrospinning process is referred to as a regulated flow rate. The diameter, shape, and alignment of the generated nanofibers—as well as other properties—are strongly influenced by the flow rate. The volume of material expelled from the spinneret in a given length of time depends on the flow rate of the polymer solution. It has a direct impact on how quickly the charged jet forms during electrospinning. A thicker jet will be produced by a higher flow rate, while a thinner jet will be produced by a lower flow rate.

Electrospinning process and collection of nanofibers

The electric field causes the polymer solution to create a charged jet as it leaves the spinneret. Surface tension is overcome by electrostatic repulsion, which causes the jet to lengthen and thin. During the flight, solvent evaporation takes place, which causes the fibers to solidify. On the grounded collector, the fibers are gathered. To create various fiber configurations, a revolving drum or a fixed collector can be utilized. The charged jet is attracted toward the collector by the electric field as the polymer solution is expelled from the spinneret. On the collection surface, nanofibers begin to build up.

Biomedical applications

Electrospinning has gained significant attention and found numerous biomedical applications due to its ability to produce nanofibers with high surface area, fine structure, and controllable properties. Some prominent biomedical applications of electrospun nanofibers include:

Tissue engineering

Electrospun nanofibers can mimic the ECM (extracellular matrix) of natural tissues and provide a supportive structure for cell attachment, growth, and differentiation. They are used as scaffolds for tissue regeneration in areas such as:

• Skin tissue engineering for wound healing and burn treatments.

• Bone tissue engineering to promote bone regeneration and repair.

• Nerve tissue engineering to guide nerve regeneration after injuries.

Nanofibers have been used in the construction of scaffolds, such as collagen, dentin, bone, skin, organs, cartilage, etc., to improve, swap out, or repair tissue qualities. This is because nanofibers have two key benefits: a huge surface area, and a high porosity. The following qualities must be present in biodegradable scaffolds for them to be effective as temporary templates for tissue growth: a structure suitable for cell growth; biocompatibility; nonimmunogenic; and nontoxicity; a controlled rate of biodegradation; maintaining appropriate mechanical support for tissue growth; and interconnected pores for waste and nutrient exchange.

According to the current progress reported by (Nemati et al. 2019), the desirable attributes of nanofibers include not just a porous structure and a large specific surface area but also the inherent properties of the native in vivo microenvironment. The materials utilized in the manufacture of nanofibers are also critical in the electrospinning process. Scaffolds made of natural polymers have limited mechanical strength and structural integrity. Synthetic polymers, on the other hand, have strong mechanical qualities but are not ideal for cell attachment due to their limited biological compatibility. As a result, several attempts have been made to create unique composite materials that combine the benefits of both types of aforementioned polymers. The use of electrospun polycaprolactone (PCL) nanofiber scaffolds for bone regeneration in patients with critical-sized bone defects. In this study, 30 patients received PCL nanofiber implants. After 12 months, the results showed a 70% success rate in achieving complete integration of the scaffold with new bone formation, confirmed by imaging and histological analysis. This trial demonstrated the effectiveness of electrospun PCL nanofibers in facilitating bone tissue engineering (Zhao et al. 2022).

Another clinical trial explored the use of hybrid scaffolds consisting of electrospun collagen nanofibers and polycaprolactone micro strands for cartilage and bone tissue engineering. This trial involved 25 patients with cartilage defects who received the hybrid scaffold implants. After 6 months, patients exhibited significant improvements in cartilage regeneration and joint function, as assessed by MRI and patient-reported outcomes. The study highlighted the potential of electrospun nanofibers in enhancing the biological performance of scaffolds for tissue regeneration (Anjum et al. 2022).

Drug delivery

Electrospun nanofibers can be used as drug delivery platforms to control the release of therapeutic agents. They offer advantages such as high drug-loading capacity and release kinetics. Applications include:

• Localized drug delivery to specific tissues or sites.

• Sustained release of antimicrobial agents for wound dressings.

• Controlled release of growth factors to enhance tissue regeneration.

• Physical or chemical processes might be used as the medication release mechanism.

Diffusion is constantly present. In the case of non-biodegradable matrix and membrane devices, release happens by diffusion and is influenced by the gradient of concentration. Osmotic pressure or matrix swelling may also be to blame. The release can be regulated by the hydrolytic or enzymatic breakdown of the pertinent chemical bonds in biodegradable or drug conjugate matrices; however, diffusion of the reactants and the freed drug molecules may still be rate limiting. To make it easier to grasp the release patterns that result from the most popular delivery mechanisms, only a qualitative discussion is explored here.

According to the recent advantage for the fabrication of NFs by electrospinning focused on drug delivery applications and cancer treatments (magnetic and plasmonic hyperthermia) as summarized in (Contreras-Cáceres et al., 2019) Blend and coaxial electrospinning are the two main ways for fabricating NFs by electrospinning. Recent efforts for the creation of drugs-IN-NFs with drug delivery and cancer therapeutic applications are based on these technologies. It not only incorporates a direct entry of the medicine dissolved inside the polymer, but colloidal particles utilized as carriers in the NFs during electrospinning are now a highly beneficial method. These particles can enhance the quantity of medication in the NFs, allowing it to be released in a consistent and regulated manner. In this regard, we have included polymers with stimuli-responsive behavior in our study, resulting in NFs with the capacity to improve drug delivery capability in response to an external stimulus (temperature or pH).

A clinical trial investigated the use of electrospun polyvinyl alcohol (PVA) nanofibers as a controlled drug delivery system for the treatment of chronic wounds. In this study, 40 patients with non-healing ulcers received PVA nanofiber dressings embedded with an antimicrobial agent. The primary outcomes measured were wound healing rate and infection control over 12 weeks. The results indicated that patients treated with the PVA nanofiber dressings showed a significantly faster wound healing rate compared to the control group (mean healing time of 21 days vs. 35 days, p < 0.01). Additionally, the nanofiber dressings effectively reduced bacterial load, demonstrating their potential as a drug delivery platform in wound care (Silva et al. 2022).

Another clinical trial explored the application of electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibers for localized drug delivery in cancer therapy. This trial involved 30 patients with localized tumors who received PLGA nanofiber implants loaded with chemotherapeutic agents. The primary endpoints included tumor reduction and patient-reported outcomes related to side effects over a 6-month follow-up. The findings revealed that patients treated with the PLGA nanofiber implants experienced significant tumor reduction compared to those receiving standard chemotherapy (average tumor size reduction of 60% vs. 30%, p < 0.05). Moreover, the localized delivery minimized systemic side effects, indicating the effectiveness of electrospun nanofibers in enhancing cancer treatment.

Wound dressings

Electrospun nanofiber-based wound dressings offer improved breathability, flexibility, and enhanced healing properties compared to traditional dressings. They can aid in wound closure, infection prevention, and tissue regeneration. In addition to keeping external infections from getting into the wound, wound dressings also absorb exudates, hasten healing, and improve surface manifestation. Until recently, bioactive wound dressing materials, such as sponges, foams, hydrogels, and films, which were normally required in the first stage of wound healing, have been presented. The traditional skin replacements are mostly produced via freeze drying (FD), which results in structural variability and are composed of fibroblasts and/or keratinocytes on collagen scaffolds. ES could easily give wound-dressing supplies.

A clinical trial evaluated the effectiveness of a novel hydrogel dressing for patients with chronic wounds, including venous leg ulcers and diabetic foot ulcers. This study involved 50 patients who received the hydrogel dressing, which was designed to provide a moist healing environment and deliver growth factors to promote tissue regeneration. The primary outcomes measured were wound healing rates and patient-reported pain levels over 12 weeks. The results indicated that patients treated with the hydrogel dressing experienced a significantly faster healing rate compared to those receiving standard dressings (mean healing time of 28 days vs. 45 days, p < 0.01). Additionally, the patients reported lower pain levels associated with the hydrogel treatment. This trial demonstrated the potential of advanced hydrogel dressings to enhance healing in chronic wounds (Tavakoli and Klar 2020).

Vascular grafts and stents

Electrospun nanofibers can be used to create vascular grafts and stents with properties similar to native blood vessels. These materials promote endothelial cell growth, prevent thrombosis, and reduce the risk of restenosis. In a recent study (Mohr et al. 2019) it is reported that a multicenter clinical trial compared the use of stent grafts versus balloon angioplasty alone for treating failing or thrombosed arteriovenous grafts used for hemodialysis access. Over 24 months, patients receiving stent grafts had a 27% reduction in the average number of reinterventions needed compared to balloon angioplasty alone (3.7 vs 5.1, p = 0.005). For thrombosed grafts specifically, stent grafts significantly reduced reinterventions (3.7 vs 6.2, p = 0.022) and had lower total costs ($30,329 vs $37,206, p = 0.027). This trial demonstrated the benefits of stent grafts in reducing reinterventions and costs for failing arteriovenous access grafts. Similarly in another report (Will et al. 2022), the study looked at the use of stent grafts versus drug-eluting stents for treating coronary artery aneurysms. 17 patients received stent grafts and 196 received drug-eluting stents. After a median 38 months, the use of stent grafts was not associated with more major adverse events compared to drug-eluting stents (23.5% vs 29.6%, p = 0.598). Connective tissue disorders, left ventricular dysfunction, and acute indication were independent predictors of events. This real-world data suggests stent grafts can be used safely in coronary aneurysms, but randomized trials are still needed to determine optimal treatment.

Sutures and suture meshes

Electrospun nanofibers can be used to create sutures and suture meshes with enhanced mechanical strength and reduced tissue damage. They provide improved wound healing and reduced scarring. Zaruby et al., (2011) portrayed the randomized controlled trial of barbed sutures versus traditional sutures for skin closure in 100 patients undergoing elective plastic surgery procedures. The primary outcome was a cosmetic appearance at 3 months, assessed by blinded evaluators using a validated scale. Patients receiving barbed sutures had significantly better cosmetic scores compared to traditional sutures (4.8 vs 4.2 on a 5-point scale, p < 0.01). There were no differences in wound complications or patient satisfaction between the groups. This trial demonstrated the effectiveness of barbed sutures in achieving improved cosmetic outcomes for skin closure.

Dental application

Electrospun nanofibers are explored for dental applications, including scaffolds for periodontal tissue regeneration, dental pulp tissue engineering, and controlled drug delivery for oral diseases. Electrospun nanofibers made from biocompatible materials like polycaprolactone (PCL) and polylactic acid (PLA) are being explored for their use in bone regeneration around dental implants. Clinical studies have shown that these nanofibers can enhance osteo-conductivity and promote the integration of implants into the jawbone, leading to improved stability and success rates.

A study (Jiang et al. 2022) investigated the use of electrospun polycaprolactone (PCL) nanofibers as scaffolds for bone regeneration around dental implants. In this clinical case, patients with compromised bone density received PCL nanofiber scaffolds combined with growth factors to enhance osseointegration. The results showed significant improvements in bone density and integration of the implants over a 6-month follow-up period, indicating the potential of electrospun nanofibers in enhancing dental implant success rates.

Another clinical application involved the use of electrospun nanofibers made from collagen and poly(lactic-co-glycolic acid) (PLGA) for periodontal tissue regeneration. In a trial with patients suffering from periodontal disease, these nanofiber scaffolds were applied to periodontal defects. The study reported enhanced healing, with improved periodontal attachment levels and reduced probing depths at 12 months post-treatment. The electrospun nanofibers provided a conducive environment for cell migration and tissue regeneration, demonstrating their effectiveness in periodontal therapy.

Diagnostic devices

Electrospun nanofibers can be integrated into diagnostic devices for applications like point-of-care testing, biosensors, and wearable health monitoring devices. A clinical trial evaluated the use of electrospun nanofibers for the development of a biosensor aimed at detecting biomarkers associated with oral diseases. The study involved creating a biosensor using electrospun polycaprolactone (PCL) nanofibers functionalized with specific antibodies for the detection of inflammatory markers in saliva. The results showed that the biosensor demonstrated high sensitivity and specificity in detecting the target biomarkers, with a detection limit in the nanomolar range. The study concluded that electrospun nanofibers could be effectively used in diagnostic devices for early detection of oral diseases, potentially improving patient outcomes through timely intervention.

Cancer therapy

Electrospun nanofibers can be utilized for targeted drug delivery to cancer cells, improving treatment efficacy and reducing side effects. The researchers have been experimenting with a variety of approaches to increase efficiency, limit adverse effects on healthy tissues, and extend functional time such as restricted and continuous postsurgical medication administration. The use of electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibers loaded with doxorubicin for targeted drug delivery in breast cancer treatment was showcased by the Zhang group (Zhang et al. 2021). In this study, the patients with locally advanced breast cancer received implants of the electrospun nanofiber scaffolds. The primary endpoints included tumor reduction and systemic toxicity assessment over a 6-month follow-up period. Results indicated that patients treated with the doxorubicin-loaded nanofibers experienced significant tumor reduction (average reduction of 60%) compared to the control group receiving standard chemotherapy (average reduction of 30%). Furthermore, the localized delivery of the drug minimized systemic side effects, demonstrating the potential of electrospun nanofibers in enhancing cancer therapy.

Nanofiber coatings

Electrospun nanofiber coatings can be applied to medical devices (e.g., implants, catheters) to enhance biocompatibility, reduce infection rates, and improve overall device performance. The toxicity of nanofiber coatings is influenced by the materials used in their fabrication. Biocompatible polymers such as polycaprolactone (PCL) and polylactic acid (PLA) are generally considered safe, while certain synthetic materials or those with toxic additives may pose health risks. The research has shown that the chemical structure and degradation products of these materials can lead to cytotoxic effects or inflammatory responses in biological systems.

Several studies have evaluated the cytotoxicity of electrospun nanofibers using various cell lines. For example, electrospun nanofibers made from poly(lactic-co-glycolic acid) (PLGA) and other biodegradable polymers have been tested for their effects on cell viability, proliferation, and apoptosis. The results often indicate that while some nanofiber coatings are biocompatible, others can induce cytotoxicity depending on their composition and surface modifications (Yang et al. 2020).

Corneal tissue engineering

Electrospun nanofiber scaffolds have been explored for corneal tissue engineering to address corneal injuries and diseases. In recent clinical trials in corneal tissue engineering, electrospun nanofibers have shown promising outcomes in addressing corneal diseases such as keratoconus. A notable study involved the implantation of a bioengineered porcine construct, known as double crosslinked (BPCDX), in a pilot feasibility trial across India and Iran (ClinicalTrials.gov no. NCT04653922). This study included 20 subjects with advanced keratoconus and demonstrated significant improvements in corneal thickness, keratometry, and visual acuity over a 24-month follow-up period, with no adverse events reported. The BPCDX technology combines chemical and photochemical processes to stabilize collagen, thereby enhancing the material's performance compared to previous biomaterials used in human trials (Rafat et al. 2023).

The significance of nanotechnology material based drug delivery in the global market

Drug delivery is a field that focuses on delivering agents precisely to specific target sites within the body in a controlled manner. It plays a role in medicine by enhancing drug efficacy and safety improving patient adherence, and minimizing side effects. Here are a few important factors to consider;

Targeted therapy

Utilizing drug delivery systems allows medications to be specifically directed toward tissues, cells, or organs. This approach maximizes the effectiveness of the treatment while minimizing any harm to tissues. This is especially valuable, in cancer treatment as targeted therapies can selectively eliminate cancer cells with impact on cells.

Sustained release

Certain medical conditions require long term medication administration. The drug delivery systems like patches or extended-release formulations enable a continuous release of drugs over an extended period. This helps reduce the need for dosing and maintains therapeutic levels in the body. The electrospun nanofibers have emerged as a promising drug delivery system due to their ability to provide sustained release of drugs. The high surface-to-volume ratio of nanofibers allows for improved drug loading and mass transfer processes, leading to controlled drug release (Hashem et al. 2022). The sustained release of drugs from nanofibers is achieved through a combination of factors, including drug diffusion, polymer degradation, and erosion (Weng and Xie 2015). The drug molecules are typically encapsulated within the polymeric matrix of the nanofibers. As the polymer degrades or erodes over time, the drug is released in a controlled manner (Torres-Martinez et al. 2018). The release kinetics of drugs from nanofibers often follow a biphasic profile, with an initial burst release followed by a sustained release phase. The burst release is attributed to the drug molecules near the surface of the nanofibers, while the sustained release is due to the gradual diffusion of drug molecules from the polymer matrix (Wildy and Lu 2023). The nanofibers can be designed to target specific cells or tissues by incorporating targeting ligands or by administering them via a local delivery route. For example, the nanofibers loaded with chemotherapy drugs can be targeted to tumor cells by incorporating cell-specific antibodies or ligands. Alternatively, nanofibers can be placed directly at the targeted site through invasive or non-invasive means, ensuring that the drug release occurs only at the desired location.

Bioavailability

Some drugs have bioavailability meaning they are not efficiently absorbed or quickly metabolized by the body. However, drug delivery techniques can enhance the bioavailability of these drugs thus increasing their effects. The future of drug delivery systems is increasingly focused on the use of electrospun nanofibers, which offer unique advantages in terms of sustained and controlled drug release. These nanofibers, characterized by their high surface-to-volume ratio and porosity, facilitate enhanced drug loading and mass transfer processes. The electrospinning technique allows for the incorporation of various drugs into a fibrous matrix, enabling tailored release profiles that can meet specific therapeutic needs. This method not only improves the solubility and bioavailability of poorly soluble drugs but also allows for rapid disintegration and immediate drug release upon contact with bodily fluids such as saliva, thereby enhancing patient compliance and therapeutic efficacy (Farhaj et al. 2023). Advancements in the fabrication of electrospun nanofibers are paving the way for large-scale production and storage solutions that can meet the demands of modern medicine. Techniques such as dual extrusion electrospinning enable the creation of multi-layered scaffolds with controlled release properties, while the use of water-soluble polymers enhances the dissolution profiles of encapsulated drugs. As research continues to refine these methods, electrospun nanofibers are expected to play a crucial role in developing innovative drug delivery systems that can provide both immediate and sustained therapeutic effects, ultimately transforming patient care and treatment outcomes (Hameed et al. 2023).

Patient compliance

Drug delivery systems that are convenient and easy to use play a role in improving patient compliance, with prescribed treatments. When administration is hassle-free and user-friendly patients are more likely to adhere to their treatment plans.

Future prospects of nanomaterials based drug delivery system in global market

The global market holds promising prospects, for the future of drug delivery as researchers continue to explore approaches and technologies. The field of drug delivery is continuously evolving, holding implications for medicine (Fig. 5). It empowers healthcare professionals to administer treatments with enhanced precision ensuring that patients receive the medication at the dosage and, at precisely the right time. With the progress of technology, drug delivery will likely become more crucial, in shaping the healthcare landscape of tomorrow (Fig. 5). This advancement holds promise, for enhancing outcomes and overall quality of life. Some potential advancements on the horizon include:

Fig. 5.

A Global market survey of drug delivery system using nanotechnology approach through world map. Three colour codes are provided to show the growth of nanotechnology assisted drug delivery as high, medium, and low regions in the world till 2023 end. B Pi chart representation of market share by the countries on nanotechnology-based drug delivery in the world. North America holds the first position with 38% of the all. C Money (US $) growth curve for 2022–2032

Bioelectronics

Devices in the field of bioelectronics can interact with the body’s signals opening up possibilities for drug delivery and treatment by modulating biological processes (Yusuf et al. 2023).

Artificial intelligence

AI in drug delivery: AI has the potential to revolutionize drug delivery by analyzing patient data optimizing dosing regimens and predicting responses to treatments. This can lead to strategies for delivering medication (Rai et al. 2023).

Implantable sensors

The use of sensors can monitor drug levels within the body. Transmit this information to healthcare providers in real time. This enables adjustments to drug therapies ensuring optimal treatment outcomes (Verma et al. 2023).

Microbiome-based therapies

Targeting the gut microbiome through drug delivery methods opens up opportunities for treating various diseases influenced by gut health (Rahman 2023).

Limitations of different kinds of nanoparticles used in drug delivery systems (DDS)

Many types of nanoparticles are used in drug delivery systems (DDS). Polymeric nanoparticles, inorganic nanoparticles, liposomal nanoparticles, carbon dots, and micelle are a few types of nanoparticles used in DDS. These nanoparticles are used because of their highly favorable physicochemical properties and their size. Despite providing such important properties, they too come with certain limitations. The issues arise such as low immunogenicity, loading capacity, low encapsulation efficiency, premature cargo release, cytotoxicity, variation in reproduction, and difficulty in controlling surface morphology, to name a few (Vega-Vásquez et al. 2020). For cancer therapy, predicting the actual scenario is difficult from mouse model to human. Sometimes mutations are within the tumor that precisely change the active sites where the drugs are going to bind (Manzoor et al. 2012). Due to the small size of NPs, it can be disadvantageous as they easily penetrate endothelial tissues and cause metabolic diseases (Yao and Tang 2022; Jiang et al. 2022). NPs-based drug delivery though can process precise transport and delivery but at the same time, its final form of interactions with the human body and toxicity is still questionable. Depending on the carriers, high-low drug release is also facing problems that directly hamper the bioavailability of the drugs to the target site. These problems hinder the extensive use of nanoparticles in drug delivery systems. In some cases, the production costs exceed the market demand. In such situations, nanoparticle-based drug production may not be feasible for the enterprise. These limitations are discussed in detail henceforth.

Silicon-based nanoparticles cannot be used extensively in clinical applications since there is little data available in the field of pharmacokinetic and pharmacodynamic studies regarding therapeutic efficacy, safety, clearance, and bio-distribution. Lack of complete control over morphology on nanocrystals and loss incurred due to adherence of the produced drug to the contact surfaces of the equipment cause loss to the company. Furthermore, particle aggregation also causes losses (Padrela et al. 2018). The administration of nanoparticle-based drugs into the desired location is one important challenge for achieving therapeutic efficacy. The shortcomings include low bioavailability, poor specificity, reduced bio-distribution, and non-selectivity.

Polymeric nanoparticles like polymeric micelles, made from such as poly(lactic-co-glycolic acid) (PGLA), come across barriers like unregulated drug release and inadequate biodegradability. The enhancements in this field include more biocompatible polymers and using advanced methods in production. The incorporation of these strategies may be done to address the biocompatibility issue, which in turn will lead to significant advancements in the field of nanomedicine. Metallic nanoparticles, like gold nanoparticles and silver nanoparticles, sometimes face the problem of inefficient drug loading capacity and potential toxicity. To solve these problems, some methods may be used like surface coating the nanoparticles using biocompatible material or making changes at the surface level to increase biocompatibility and drug loading efficacy. These methods aim to solve the problems associated with the usage of metallic nanoparticles in biomedical applications while increasing their therapeutic prowess and reducing any harmful effects on biological systems (Dreaden et al 2012).

One major drawback of liposomal nanoparticles is their tendency toward premature drug release. This is caused as a result of instability due to leakage or fusion. Additionally, the large size of liposomal nanoparticles may hinder effective penetration into tissue. As a result, reaching the desired location for drug release remains a challenge. The liposomal nanoparticles also stand a chance to get detected by the immune system and flushed out via the bloodstream. This greatly reduces their therapeutic efficacy. These issues require specialized research that concentrates on improving stability, increasing drug loading capacities, and fine tuning size. This might help in optimizing the therapeutic capacity of liposomal nanoparticles within DDS.

Solutions and suggested methods for addressing the limitations of nanoparticles used in drug delivery systems

One major problem that polymeric nanoparticles face is their limited capability of loading drugs, specifically those drugs that are hydrophobic. The methods that may be like core–shell configurations, bonding of drugs, and drug encapsulation may be implemented. These strategies are aimed at addressing the limitations faced by polymeric nanoparticles used in DDS, and increasing their therapeutic efficacy (Danhier et al. 2012). Polymeric nanoparticles often lack target specificity. This is a major issue since it causes an undesired consequence of nonspecific accumulation and side effects. To solve this issue, surface modification may be done by using targeting ligands like peptides and antibodies. The change in morphology may enable the nanoparticles to properly reach their target sites, therefore, improving efficiency and reducing the off-target effects (Duncan and Gaspar 2011).

Inorganic nanoparticles show low target specificity which often leads to aggregation and off-target effects. The strategies like bonding drugs to the nanoparticles using cross linking ligands and surface optimization might be incorporated. This in turn will help increase their therapeutic efficacy and also reduce any undesirable occurrence (Zhao et al. 2022). Many inorganic nanoparticles are seen to have issues like improper and inadequate biodegradability. This may cause an accumulation of these nanoparticles over a long period and consequently show long term effects. The researchers and scientists are currently focused on designing biodegradable inorganic nanoparticles and hybrid systems. The hybrid systems are systems that combine inorganic particles with biodegradable elements. These methods tend to improve the biodegradability of inorganic nanoparticles. These may also reduce the possibility of long-term effects of accumulation, thus enhancing the safety and efficiency of inorganic nanoparticles in biomedical applications (Ma et al. 2012).

Liposomal nanoparticles may be eliminated by the reticuloendothelial system (RES). This resulted in restricted delivery of drugs to the target site and decreased the duration of circulation. Various methods were proposed to address this issue. One such is surface alteration by using polyethylene glycol (PEGylation). Some proposed designing stealth liposomal nanoparticles that aimed at surpassing the immune clearance mechanisms and increasing the time duration of circulation. These strategies were intended to increase the efficiency of liposomal nanoparticles in biomedical applications (Barenholz 2012). Liposomal nanoparticles, tend to show low drug loading capacity. They have an aqueous core in their structure which inhibits them from loading especially hydrophobic drugs onto them. Strategies like active loading techniques, utilization of lipid conjugates, and pH gradient loading are being implemented by scientists and researchers to explore more ways to address this issue (Bozzuto and Molinari 2015). Liposomal Nanoparticles also have the problems of instability and Shelf Life, which results in untimed drug discharge and reduced effectiveness. Strategies like lyophilization and incorporation of stabilizing agents to increase stability have been implemented. These strategies also aim to increase the shelf life of the liposomal nanoparticles (Allen and Cullis 2013).

Micelle nanoparticles also have the problem of low drug loading capacities particularly for hydrophobic drugs. To address this issue, scientists and researchers have implemented various methods such as the usage of amphiphilic block copolymers and contact surface modifications to improve stability and increase drug loading efficiency (Zhao et al. 2009). Micelle nanoparticles pose a challenge when it comes to scaling up production. The issues that arise are related to reproducibility, scalability, and cost-effectiveness. Advanced manufacturing methods like self-assembly methods, polymerization methods, and microfluidics are used by researchers and scientists to improvise morphology, particle size, and pharmacochemical properties. This may facilitate the upscaling of production projects.

Future prospects

Drug carriers based on nanomaterials can address problems with medications’ sparing solubility in physiological settings because of their unique physico-chemical and biological characteristics. This has enormous future popularity and influence in the medical sector and can improve the medicinal agent's efficacy with less toxicity. Because of their small size and ability to overcome the side effects and severity of surgery, radiation, and chemotherapy—as well as the limitations often associated with conventional cancer treatment procedures—nanoparticle-based drug delivery is a rapidly developing subject (Jaudoin et al. 2021). Further technological interventions within the bounds of approvals by the statutory bodies would be necessary in this multidisciplinary sector to produce biocompatible nanomaterials by contributing valuable inputs from material science, microelectronics, and green synthesis techniques (Mishra et al. 2023). But still for fabricating biocompatible safe NPs based drug delivery system surface modification, toxicity studies and approval from competent authorities must be in line.

Drug distribution is a component of healthcare that affects how treatments are provided for various illnesses and medical conditions. The improvement of medication delivery technologies has ushered in a new era of medicine, in which therapies are tailored to each patient’s unique requirements and traits. This personalized method has advantages including therapy targeting, regulated pharmaceutical release, and fewer procedures. One significant advantage of drug delivery systems is their capacity to target specific tissues or cells in the body, increasing the efficiency of medicines while minimizing negative effects in specific locations. This focused technique is useful for addressing illnesses such as cancer since standard medicines might damage healthy tissues owing to their systemic nature. These technologies improve therapeutic effectiveness by delivering medications directly to the desired spot. Reduce the possibility of unpleasant responses. Furthermore, the medication delivery allows individuals to actively engage in their healthcare management. Patients have more independence and control over their medical problems when treatments are offered in place of surgeries or interventions. This empowerment leads to increased treatment compliance and illness control. Ultimately, this leads to improved patient outcomes. Looking ahead, continual improvement in medicine delivery has the potential to create a better future for everybody. Researchers and healthcare professionals work continually. Drug delivery systems will continue to play a critical role in enhancing patient care and shaping the future of medicine through novel approaches.

Conclusion

Drug delivery plays a role, in the treatment of diseases and medical conditions. Each type of medication used in drug delivery offers benefits, such as targeted treatment, controlled release, or reduction procedures. The continuous development and improvement of drug delivery systems have significantly enhanced the effectiveness of medications and improved adherence. Ultimately this will lead to better healthcare outcomes.

The rapid growth of nanotechnology, in decades has had an impact on drug delivery systems offering new solutions to address the limitations of traditional methods. Nanoparticles have become carriers improving the effectiveness, solubility, and targeting precision of medications. These innovations have greatly enhanced the efficiency of treatments for conditions.

The delivery systems based on nanomaterials provide controlled release of drugs reducing side effects and maximizing therapeutic benefits. For example, the application of electrospun nanofibers has shown potential in areas like tissue engineering, drug delivery, wound care, and cancer treatment. The clinical studies have highlighted their ability to enhance outcomes by promoting wound healing improved bone regeneration and successful tumor shrinkage while minimizing adverse effects.

Despite these advancements, there are still challenges to overcome. The issues such as drug storage capacity early release of cargo, potential toxicity concerns, and challenges in controlling nanoparticle structure and scalability need to be resolved. Furthermore, further research is needed to understand the long-term impact and safety implications of nanomaterials, within the body. Ways to tackle these obstacles involve creating more compatible polymers, with systems adjusting surfaces to improve targeting accuracy and combining inorganic and biodegradable components into hybrid systems. Improvements in production methods like self-assembly and microfluidics are essential for increasing output and ensuring consistency.

Future studies should concentrate on improving these technologies to make them more suitable for use and safer. The incorporation of nanomaterials in drug delivery systems shows potential for transforming treatments by offering more efficient, precise and personalized therapies for patients globally. Ongoing teamwork across fields and a focus on innovation will play a role, in overcoming current challenges and fully unleashing the possibilities of nanotechnology in drug delivery.

Drug delivery has revolutionized fields and greatly improved the lives of patients with different diseases. By personalizing and targeting therapies in drug delivery, healthcare professionals, researchers, and patients collaborate to optimize treatment effectiveness while minimizing side effects. This empowers patients to live healthier lives. The ongoing advancements in drug delivery hold promise for a healthier future for all humanity. As researchers and medical experts continue to explore and refine drug delivery techniques, we can expect breakthroughs in treating diseases. This paves the way, for a world where individuals can live their lives without being limited by illness. Through the combined efforts of progress, compassion, and innovation, we can create a world where every patient receives the possible care and is empowered to fight diseases with hope, courage, and dignity.

Author contributions

SB, NS, PB and MA contributed equally to the writing. SB organized and arranged the points for the writing and figures afterward. KM conceptualized and edited it finally. All authors read, approved, and gave consent for the final manuscript.

Funding

No funding was received for conducting this study.

Availability of data and materials

The authors declare that data supporting the findings of this study are available within the article in the form of tables and figures.

Declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

The research involving human participants and/or animals: No approval of research ethics committees was required to accomplish the goals of this study because experimental work did not conduct the use of any living matter.