Review on Electrospray Nanoparticles for Drug Delivery: Exploring Applications

Abstract

Electrospraying has emerged as a versatile technique in the pharmaceutical field due to its potential in drug delivery and formulation. With its advantages of cost-effectiveness, reproducibility, ease of operation, and scalability, electrospraying offers numerous benefits for pharmaceutical applications. Notably, the production of nanoparticles using electrospraying provides unique properties, including small size, drug encapsulation capabilities, biocompatibility, and scalability. Electrospray nanoparticles have demonstrated significant promise in various drug delivery routes, such as oral and topical administration. These nanoparticles enhance drug stability, protection, and permeability, effectively overcoming limitations associated with these routes. Moreover, electrospray nanoparticles have proven valuable in targeted drug delivery, improving drug bioavailability and efficacy. Their ability to penetrate tissues and cells enables enhanced drug delivery to specific sites within the body. Additionally, electrospray nanoparticles can be tailored with targeting ligands or responsive components for controlled release and combination therapy, exhibiting successful applications in cancer treatment and neurological disorders. Therefore, electrospray nanoparticle technology shows great promise in biomedical applications, offering a versatile platform for targeted drug delivery and therapeutic interventions. This comprehensive review examines the various drug delivery applications of electrospraying and provides insights into its possibilities and challenges. The paper discusses the principles, methods, and parameters of electrospraying, while also exploring its use in fabricating drug delivery systems, addressing poorly soluble drugs. By synthesizing the findings from multiple studies, this review offers a comprehensive understanding of electrospraying’s current state and potential in the pharmaceutical industry.

1. Introduction

Nanotechnology is a rapidly evolving discipline that enables researchers to develop a wide range of biomedical materials with the potential to recreate the complex structure and organization found in biological tissues within artificial or synthetic materials at the nanometre scale. These materials exhibit desirable properties such as biocompatibility, nontoxicity, and the ability to sense and respond to environmental stimuli^{1, 2}. Nanomaterials have a high surface-to-volume ratio and can be made to be permeable through various channels and membranes. This makes them an excellent material for targeted drug delivery applications³. Hence, nanomaterials have gained significant attention in drug delivery applications due to their desirable properties, including variable size distribution (10-100 nm), high porosity, and low density^4–6. Additionally, at the nanoscale, particles exhibit unique properties that differ from their bulk counterparts. Nanomaterials present a host of advantages when employed in drug delivery applications. Their diminutive size permits precise control over drug release, enabling the directed delivery of medications to specific cells or tissues while minimizing unintended side effects. In addition, nanomaterials can enhance drug solubility, stability, and bioavailability, thus augmenting the overall therapeutic effectiveness of pharmaceuticals. Furthermore, their capacity to encapsulate a wide array of drugs, including those with limited water solubility, broadens the spectrum of treatable diseases. Moreover, nanomaterials can be tailored with surface modifications, such as ligands or antibodies, to actively target specific (e.g., diseased) cells, thereby enhancing the specificity and efficiency of drug delivery. Such nanomaterials are widely studied to enhance efficacy of cancer therapeutics⁷. The advantageous properties have led to the extensive research utilization of nanomaterials in additional areas such as imaging, diagnostic tools, tissue engineering, gene therapy, vaccines, and neuroscience applications.

Nanoparticles can be consistently produced in large quantities using cost-effective one-step techniques^{8, 9}. For instance, polymer nanoparticles can be synthesized through different methods, classified into top-down and bottom-up processes^{8, 9}. The bottom-up approach involves the synthesis of nanoparticles through chemical reactions between atoms, ions, or molecules. Wet chemical synthesis methods, such as sol-gel, micro-emulsion, hydrothermal synthesis, co-precipitation, and electrospinning, fall under the bottom-up category^{10, 11}. On the other hand, top-down approaches utilize mechanical methods to break down bulk materials into nanoparticles ¹¹. Mechanical milling, laser ablation, ion implantation, electron beam lithography, and chemical etching are examples of top-down processes^{6, 12–15}. Hybrid approaches combining both top-down and bottom-up methods are also employed to produce nanomaterials¹¹. Furthermore, synthesis methods can be categorized as chemical (e.g., polymerization, oxidation, reduction), biological (e.g., plant extract, bacteria, fungi, algae), mechanical (e.g., ball milling, mechanical attrition, mechanical grinding), and physical (e.g., thermal evaporation, thermal pyrolysis, physical vapor deposition, laser ablation, nano spraying, spinning)¹⁶. Mechanical methods are considered a subset of physical methods. Laser ablation and spinning are widely used physical methods due to their ability to produce highly pure nanoparticles of desired sizes^{17, 18}. Both this method come with disadvantages like may require high energy input, limited to certain materials, chances of contamination, some processes are not scalable at large scale, may require complex synthesis techniques, etc (Table 1).

Table 1:-.

Various method of preparation of nanoparticles

Methods	Advantages	Disadvantages	Application	Synthesis type	References
Chemical Precipitation	- Simple and cost-effective. - Suitable for large-scale production. - Versatile for various materials.	- Limited control over size/shape. - Polydispersity in particle size. - Often requires post-synthesis steps	- Catalysts, pigments, drug delivery.	Bottom-Up	19, 20
Sol-Gel Synthesis	- Precise control over composition. - Produces homogeneous nanoparticles. - Suitable for doping and hybrid materials.	- Requires specialized equipment. - Relatively slow process. - Hydrolysis/conden sation reactions.	- Thin films, coatings, ceramics.	Bottom-Up	21, 22
Hydrothermal Synthesis	- High-temperature and pressure conditions. - Improved crystallinity and purity. - Control over size and shape.	- Limited to certain materials. - Lengthy reaction times. - Energy-intensive.	- Nanowires, metal oxides, ceramics.	Bottom-Up	23-25
Chemical Vapor Deposition	- High precision in size and structure. - Uniform deposition on substrates. - Suitable for high-purity materials.	- Complex and expensive equipment. - Limited to thin films. - High energy consumption.	-Biomedical application	Bottom-Up	26
Green Synthesis	- Environmentally friendly. - Mild reaction conditions. - Uses natural or biological sources.	- Limited to specific materials. - Variable control over properties. - Longer synthesis times.	- Biomedical applications, catalysis.	Bottom-Up	27-29
Microemulsion Method	- Excellent size and shape control. - High stability of colloidal solutions. - Suitable for hydrophobic materials.	- Requires surfactants and co-surfactants. - Limited scalability. - Complex process optimization.	- Drug delivery,	Bottom-Up	30, 31
Lithography	- Precise control over size and shape. - High resolution patterning. - Scalable for nanoscale devices.	- Limited to specific materials. - Complex lithographic processes. - Expensive equipment and cleanrooms.	- Drug delivery.	Top-Down	32
Ball Milling	- Effective size reduction. - Suitable for various materials. - Scalable for bulk production.	- Limited control over particle shape. - May introduce impurities. - Mechanical stress on particles.	- Nanocomposites, drug delivery.	Top-Down	33, 34
Template-Assisted	- High precision in nanoparticle design. - Control over size, shape, and structure. - Reproducible and uniform results.	- Complex template fabrication. - Limited to templatable materials. - Removal of templates required.	- Drug delivery.	Top-Down	34-36
Electron Beam Lithography	- Ultra-high resolution patterning. - Nanometer -scale feature control. - Suitable for various substrates.	- Requires expensive equipment. - Time-consuming and serial process. - Limited scalability for large areas.	- Nanoelectronics, photonics.	Top-Down	37, 38

Two additional, widely used techniques for producing nanoparticles are electrospinning and electrospraying, which both utilize an electric field to generate a charged jet of polymer or solution, resulting in the formation of nanofibers or nanoparticles on a substrate¹⁸. Electrospinning is primarily used for the fabrication of nanofibers, while electrospraying is utilized for the fabrication of nanoparticles^39–42. These techniques offer advantages such as scalability, reproducibility, high encapsulation efficiency, and drug specificity through active surface absorption, binding, or complexation.

This review will focus on electrospraying, which has over the past few years emerged as a promising technique with diverse applications in medical field. Electrospraying involves the formation of fine droplets through the application of an electric field to a liquid, enabling the fabrication of various drug delivery systems with precise control to address the challenges associated with poorly soluble drugs. The polymer solutions used can be either, natural, synthetic, or a combination of the two. Although the technique is widely used and studied, a deeper understanding of the fundamental mechanisms and processes involved is still very limited. Despite numerous studies exploring different aspects of technique, there are still many unanswered questions about the factors that influence the properties of the resulting nanoparticles, such as their diameter, alignment, and morphology. With continued advancements, electrospraying holds significant promise for the development of innovative pharmaceutical formulations and therapies. However, this method gives unique advantages compared to the methods listed above, such as uniform particle size, high drug loading, controlled surface properties, ability to form multi-layer nanoparticles in one step, rapid production, high purity, and material versatility. This review will review principles, particle characteristics, and the influence of different process parameters on nanoparticle morphology. Further, we will show an overview of the biomedical applications and significance of electrospinning, particularly in the following drug delivery areas: targeted delivery, topical applications, oral delivery, and injectable delivery. By examining these applications, the review underscores the potential of electrospinning in advancing drug delivery systems across different administration route highlighting the versatility of electrospraying technique.

2. Electrospraying

2.1. Working principle

Electrospraying entails the application of a high voltage to a polymeric solution, which is then forced through an electrically charged jet, resulting in the formation of nanoparticles^43–47. This process is also called as Electrohydrodynamic atomization (EHDA). A typical setup for electrospraying consists of (1) a high voltage electric system, (2) a syringe pump, (3) a syringe equipped with a needle of specific pore diameter, and (4) a metal collector (Fig 1).

Figure 1: -.

Schematic Representation of nanoparticles being formed during Electrospraying process (A)⁴⁸, types of nanoparticles (B)⁴⁹ can prepare and various application in biomedical application(C).

The precise control of nanoparticle size and morphology can be achieved by adjusting key process parameters, including the applied voltage, solution properties, and nozzle geometry^50–55. The use of a high voltage system, typically ranging up to 50 kV, induces repulsive forces that overcomes the surface tension of the polymer solution. This leads to the formation of a jet or cone-shaped structure known as the Taylor cone (Fig.1A). With further increases in the electric field, the Taylor cone disintegrates into highly charged droplets, resulting in the formation of nanoparticles^{47, 56}.

The use of a syringe pump unit is essential for controlling the flow of the polymer solution in the electrospraying process. The syringe pump holds the syringe with the needle and enables precise control of the solution flow rate. It provides the flexibility to accommodate single, double, or multiple syringes, allowing for simultaneous or individual operation. By adjusting the flow rate, researchers can achieve the desired morphology of the nanoparticles. The selection of a suitable syringe with a specific pore diameter is crucial in determining the size and morphology of the particles, since the size of the needle pore affects the formation and size distribution of the ejected droplets, ultimately influencing the resulting nanoparticles^{31, 32}.

The collecting system gathers the nanoparticles expelled from the syringe (Fig. 1)⁵⁷. The choice of collector system significantly impacts the morphology of the nanoparticles. Two primary types of collectors are commonly used: stationary and rotating collectors^58–63. Stationary collectors typically consist of flat plates, while rotating collectors can take the form of disks, mandrels, or drums, offering a wide range of dimensions. The collector design influences the deposition pattern and alignment of the nanoparticles, thereby influencing their final morphology. Thus, the syringe pump unit, with its controlled flow rate and selection of appropriate syringe and needle, along with the choice of collector system, all play a crucial role in achieving the desired size and morphology of nanoparticles during the electrospraying process.

2.2. Factors affecting nanoparticle formation

The morphology of nanoparticles can be controlled by parameters from within three main groups: solution parameters, process parameters, and environmental parameters (Table 2). By carefully adjusting and optimizing these parameters, precise control over the morphology of nanoparticles in the electrospraying process can be achieved. Understanding the relationships between these parameters is essential for tailoring the desired nanoparticle characteristics for various applications in fields such as drug delivery and biomedical engineering.

Table 2:-.

Factor affecting formation of nanoparticles and there chareteristics⁷³.

Parameters		Characteristic
		Increases	Decreases
Equipment	Electric Potential	High electrical potential (greater than 10 kV) results in the formation of particles of smaller diameter	Low electric potential (less than 10 kV). There is no formation of Taylor Cone or particles of larger diameter
	Flow Rate	At a high flow rate, (≥1 mL/h) it can lead to the formation of large size particles (≥1 μm)	At low flow rate (<1 mL/h) and increasing the electrical conductivity can lead to smaller particles (<1 μm)
	Collector distance	A large distance (15–20 cm or greater) provides more spherical morphology and more volatilization of solvent	Short distance (5–14 cm) results in collapse of the particle
Solution	Concentration	High concentrations tend to form larger particles	Low concentrations tend to form smaller particles
	Viscosity	Increases if the concentration of the polymer is increased and larger particles are obtained	By increasing the voltage and the flow rate, the viscosity decreases and smaller particles are obtained
	Density	Thicker Taylor cone, larger inertial force, therefore droplets are larger	Smaller diameter Taylor cone decreasing fluid resistance, small particles are formed
	Electrical conductivity	If is high, exceeds surface tension and smaller particle diameter will be obtained	If is low, higher surface tension, generates larger particles
Environmental	Relative humidity	If ≤30%, all the solvent is volatilized and completely dry polymer reaches the collector. Smaller particles are obtained	If >30%, no uniform particle diameter and not defined morphology. Larger particles are obtained

Solution Parameters refer to the characteristics of the polymer solution used in the electrospraying process. They include the polymer concentration, solvent type, viscosity, surface tension, and conductivity^{64, 65}. The polymer concentration affects the size and morphology of the nanoparticles, where higher concentrations typically lead to larger particle sizes. The choice of solvent influences the solution properties and can affect the droplet formation and drying kinetics⁶⁶. Varying the viscosity of the solution can impact the jet formation and the resulting particle size⁶⁷. Surface tension and conductivity also play a role in droplet formation and the overall electrostatic forces involved⁶⁸.

Process parameters are related to the electrospraying setup and conditions. They include applied voltage, flow rate, needle-to-collector distance, and nozzle geometry^{64, 69}. The applied voltage determines the electric field strength, affecting the droplet formation and the resulting particle size⁶⁹. The flow rate of the polymer solution controls the rate of droplet ejection, influencing the size distribution of the nanoparticles⁷⁰. The distance between the needle and the collector affects the flight time of the droplets, which can impact the drying process and particle morphology⁷¹. The geometry of the nozzle, such as pore diameter or shape, also affects droplet formation and the resulting particle morphology⁴⁰.

Environmental parameters refer to the conditions in the surrounding environment during the electrospraying process. These include temperature, humidity, and air flow. Environmental conditions can influence the drying kinetics of the droplets, affecting the particle size and morphology⁷². Temperature and humidity levels can affect the evaporation rate, leading to variations in particle size. Additionally, air flow can impact droplet flight and deposition patterns on the collector surface^{70, 72}.

By systematically investigating and optimizing these parameters, researchers can achieve precise control over the electrospraying process, leading to the production of nanoparticles with tailored properties and morphology (Fig 1).

The properties of the solution being used for electrospraying, including viscosity, conductivity, and surface tension, play a significant role in determining the size, morphology, and uniformity of the resulting nanoparticles^{74, 75}.

2.2.1. Solution Parameters

The choice of solvent in the production of nanoparticles using the electrospray technique plays a crucial role in determining their formation and characteristics. Therefore, careful consideration of the solvent properties is essential to achieve desired nanoparticle formation and optimize their performance. Different solvents can affect the solubility and viscosity of the polymer solution, as well as the evaporation rate during the electrospraying process. These factors influence the size, morphology, and stability of the resulting nanoparticles^{9, 74, 76}. Further, the solvent can affect the dispersion and aggregation behaviour of the nanoparticles, as well as their compatibility with the target application or biological system^{14, 77, 78}. It is recommended to select a solvent that can effectively dissolve the polymer(s) and additive(s) to ensure a homogeneous solution. Additionally, the solvent should have the ability to completely evaporate during the process. Therefore, when choosing a solvent, considerations such as boiling point, conductivity, and vapor pressure are important. Using a solvent with a low boiling point can facilitate complete evaporation. However, if the solvent evaporates too quickly, it can lead to polymer clogging the needle, causing disruptions in the process. Hence, selecting a solvent with suitable properties is crucial. Several studies have investigated the influence of solvent selection on nanoparticle synthesis. For instance, Monfared et al. observed that solvents with higher conductivity resulted in the production of smaller and more uniform nanoparticles during electrospray processes⁷⁹. Similarly, Boda et al. found that solvent conductivity affected the size and distribution of nanoparticles formed by electrospray deposition⁹. On the other hand, Kim et al. reported that solvents with high boiling points could lead to the formation of larger nanoparticles due to slower solvent evaporation⁸⁰. Additionally, Zhang et al. highlighted the issue of nozzle clogging when highly volatile solvents were employed⁷⁴.

Viscosity is a key property influenced by factors such as the molecular weight of the polymer, solution concentration, and choice of solvent. In general, higher molecular weight or concentration leads to increased viscosity. Elevated solution viscosity can result in larger particle sizes and broader size distributions due to enhanced resistance to deformation and jet break-up . However, some studies have found that higher viscosity can also yield smaller and more uniform nanoparticles⁸¹. Solvents that exhibit stronger interactions with the polymer structure tend to produce solutions with higher viscosity. Furthermore, decreasing the temperature of the solution also increases its viscosity. As discussed previously, insufficient polymer entanglement can occur when working with a low-viscosity solution, leading to jet breakage. Therefore, manipulating the polymer concentration becomes crucial to achieving the desired solution properties. Typically, higher polymer concentrations result in larger particle sizes due to increased viscosity and surface tension⁷⁵. However, extremely high concentrations can lead to particle aggregation, affecting the uniformity and stability of the nanoparticles⁸². Optimal concentration ranges have been identified in some studies to achieve the smallest and most uniform nanoparticles^{54, 83} . Furthermore, polymers with low molecular weight are generally preferred as they have a higher tendency to form beaded nanofibers, which can subsequently be transformed into nanoparticles during the electrospraying process. This allows for greater control over the resulting nanoparticle morphology⁹. By carefully selecting the polymer concentration and molecular weight, researchers can fine-tune the electrospraying process to produce nanoparticles with the desired size and uniformity .

The choice of solvent in the polymer solution and its content can significantly impact the conductivity of the solution. Different solvents, both natural and synthetic, can exhibit varying levels of conductivity depending on the polymer used^{9, 76}. It is essential to maintain consistency in the solvent grade to achieve reproducibility in the electrospraying process. Additionally, the surface tension of the solution is influenced by various factors, including polymer concentration, solvent selection, and additives. These factors collectively affect the overall solution behavior and droplet formation. Consistency in the needle gauge is also recommended, as it can impact the surface tension and droplet formation, ensuring reproducibility in the process.

2.2.2. Effect of process parameters

Several process parameters, including voltage, needle-to-collector distance, needle translation, and flow rate, have a significant impact on the morphology of electrosprayed nanoparticles. As discussed in earlier section, the electrospraying process requires a high voltage unit to control the voltage applied to the polymer solution as it is ejected at a predetermined flow rate. Typically, a high voltage system within the range of 0 to 50 kV with a current production of 0.5 amp is utilized^{84, 85}. The applied voltage plays a crucial role in determining the size, morphology, and uniformity of the resulting nanoparticles. Higher voltages generally lead to smaller nanoparticles, but excessive voltage can cause particle aggregation⁸⁵. It is essential to apply voltage to the needle, which carries a positive charge, to overcome the surface tension and enable the accumulation of nanostructures on the negatively charged or grounded collector⁸⁶. Reversing the polarity, where the needle is negatively charged, is less common in practice.

The flow rate of the solution being electrosprayed is another parameter that influences the size and morphology of nanoparticles. Higher flow rates have been associated with larger nanoparticles and a broader size distribution⁹. Conversely, reducing the flow rate tends to result in smaller and more uniform nanoparticles⁸⁷. Additionally, the flow rate can impact the encapsulation efficiency of active ingredients within the nanoparticles. Extremely high flow rates may lead to poor encapsulation efficiency, while an optimal flow rate can enhance encapsulation efficiency⁸⁸. Moreover, elevated flow rates can contribute to increased nanoparticle aggregation during the electrospraying process, which can further affect the size and morphology of the particles⁸⁹.

Besides, the distance between the electrospray needle and the collector is a critical factor that exerts a significant influence on the size, shape, agglomeration, and deposition efficiency of nanoparticles during the electrospraying process^{14, 75, 90}. Several studies have shown that a shorter distance leads to the production of smaller, more uniform nanoparticles, while a longer distance results in larger nanoparticles with a wider size distribution^{9, 91}. When the distance is too close, nanoparticle agglomeration can occur, leading to poor deposition efficiency. Conversely, an optimal distance allows for good deposition efficiency and minimal agglomeration^{74, 79}. Moreover, varying the distance can also affect the porosity of the nanoparticles, with longer distances associated with increased porosity and shorter distances leading to decreased porosity⁹².

The translation of the needle during the electrospraying process is another factor that influences the size, morphology, deposition efficiency, and porosity of the nanoparticles. Studies have shown that moving the needle closer to the collector can result in larger nanoparticles with a wider size distribution, while moving it away can lead to smaller, more uniform nanoparticles^{64, 93}. Optimizing the translation speed of the needle can improve the deposition efficiency and achieve a more uniform deposition pattern^{9, 76}. Furthermore, the translation speed can also impact the porosity of the nanoparticles, with a faster speed associated with increased porosity and a slower speed associated with decreased porosity⁹⁴. Therefore, careful control of the needle translation is crucial for achieving the desired size, morphology, deposition, and porosity characteristics of the electrosprayed nanoparticles.

2.2.3. Effect of Environmental parameters

In addition to solution parameters and process parameters, monitoring the environmental parameters such as temperature, humidity, airflow and the pressure is the key for reproducibility as the solvent evaporation rate and solution viscosity is influenced by these parameters affecting the morphology of the of the nanoparticles. Temperature and humidity have a significant impact on solvent evaporation rate and drying time, ultimately influencing nanoparticle size and morphology. Higher temperatures and lower humidity levels promote faster solvent evaporation, resulting in smaller and more uniform nanoparticles [96]. Conversely, lower temperatures and higher humidity levels can lead to larger and more irregular nanoparticles⁷². Airflow also plays a role by influencing the direction, distribution, and drying time of electrosprayed droplets. Increased airflow generally leads to smaller and more uniform nanoparticles, while reduced airflow can result in larger and more irregular nanoparticles⁹. Additionally, the pressure of the gas used in electrospraying affects nanoparticle size, morphology, and deposition pattern. Higher pressures tend to produce larger and more uniform nanoparticles, while lower pressures can lead to smaller and more irregular nanoparticles⁷⁵. By precisely controlling parameters such as applied voltage, solution properties, and nozzle geometry, researchers can effectively control the size and morphology of nanoparticles during techniques like electrospraying and electrospinning. This control allows to produce nanoparticles with specific characteristics tailored to the desired applications. Monitoring and controlling these environmental parameters are essential for achieving consistent and desired nanoparticle characteristics during electrospraying processes.

3. Type’s polymer used for fabrication of nanoparticles

The raw materials used for the fabrication of nanoparticles vary depending on the desired properties and applications of the nanoparticles. Different polymers offer distinct advantages and can be tailored to achieve the desired functionality, making them suitable for a wide range of biomedical applications. Polymers used in electrospraying can be categorized into three types: natural, synthetic, and semi-synthetic. Natural polymers, including gelatine, chitosan, alginate, collagen, keratin, hyaluronic acid, silk, and wool, are derived from natural sources and offer advantages such as biocompatibility, biodegradability, low toxicity, and stability ^{95, 96,97, 98}. These natural polymers often exhibit good cell adhesion and can mimic the extracellular matrix, making them suitable for tissue engineering and drug delivery applications⁹⁹. Natural polymers are considered safer and less toxic than synthetic polymers, and they find widespread use as both polymers and active drug ingredients^{14, 99}.

On the other hand, synthetic polymers are chemically synthesized and offer precise control over their properties. Examples of synthetic polymers used in electrospraying include poly (lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), polycaprolactone (PCL), poly (vinyl alcohol) (PVA), and poly (vinyl pyrrolidone) (PVP)^{76, 98}. These polymers provide tuneable properties such as mechanical strength, degradation rate, and drug release kinetics, making them versatile for various biomedical applications^{100, 101}. They also offer advantages such as low cost and the ability to tailor mechanical properties, degradation rates, and melting points ^{96, 101}.

Semi-synthetic polymers are derived from natural polymers but undergo chemical modifications to enhance their properties or introduce specific functionalities. For example, cellulose derivatives, such as carboxymethyl cellulose (CMC) and hydroxypropyl cellulose (HPC), are semi-synthetic polymers commonly used in electrospraying^{90, 102–104}. These polymers combine the advantages of natural polymers with the ability to modify their characteristics for improved performance in drug delivery and tissue engineering^{105, 106}.

Polymers can also be classified in terms of their degradation nature into biodegradable and non-biodegradable polymers. Biodegradable polymers, such as poly (lactic-co-glycolic acid) (PLGA), are commonly employed in electrospraying due to their biocompatibility and tuneable degradation rates¹⁰⁷. Chitosan, a natural biodegradable polymer, is utilized in drug delivery applications owing to its biocompatibility and ability to promote cell adhesion. Poly(ε-caprolactone) (PCL), a biodegradable polyester, finds applications in tissue engineering and drug delivery due to its biocompatibility and controllable degradation rate¹⁰⁸. On the other hand, non-biodegradable polymers like polyvinylpyrrolidone (PVP) are used in drug delivery, wound healing, and nanomaterial production due to their high solubility in water and organic solvents¹⁰⁹. Polyethylene glycol (PEG), another non-biodegradable polymer, is employed in drug delivery and tissue engineering applications due to its biocompatibility and resistance to protein adsorption¹¹⁰. Additionally, non-biodegradable polymers like poly (methyl methacrylate) (PMMA) are used in drug delivery and tissue engineering applications because of their high transparency, thermal stability, and mechanical strength¹¹¹.

Polymeric materials are prominently featured in electrospraying for biomedical applications due to their versatile properties, biocompatibility, and ease of processing. These materials offer tunable characteristics, allowing researchers to tailor their mechanical strength, degradation rate, and surface functionality to specific requirements. This versatility is particularly crucial in drug delivery systems, where polymers serve as carriers for controlled release formulations, enabling targeted therapy and sustained drug release. Additionally, the ease of processing polymers through electrospraying techniques facilitates the production of particles, fibers, coatings, and scaffolds with precise morphology and size distribution. However, while polymers dominate in biomedical applications, other materials such as ceramics, metals, and biological substances are also utilized, albeit less frequently. These alternative materials may offer unique properties but may face limitations in terms of biocompatibility, processability, or tunability compared to polymers. Researchers continuously explore new materials and optimize electrospraying techniques to broaden the scope of biomedical applications.¹¹². A wide range of non-polymeric materials can also be electrosprayed to fabricate nanoparticles for biomedical applications. For example, proteins, including bovine serum albumin (BSA) and lysozyme, have been utilized in electrospraying processes¹¹³. Lipids, such as phospholipids and fatty acids, have also been employed¹¹⁴. Inorganic materials, such as metal oxides, metal nanoparticles, and silica, have been explored for electrospraying applications¹¹⁵. Moreover, biomolecules, including DNA, RNA, and peptides, have been successfully electrosprayed^{48, 116}. Additionally, drugs such as antibiotics, anticancer agents, and anti-inflammatory agents have been incorporated into electrosprayed nanoparticles for biomedical purposes^{117, 118}. These diverse materials expand the scope of electrospraying, allowing for the fabrication of nanoparticles with various compositions and functionalities.

4. Electrospray nanoparticles for biomedical application

The electrospraying nanoparticle technology has opened new manufacturing options for drug delivery applications. These nanoparticles possess various properties, including drug encapsulation capabilities, absorption, binding, complexation, biodegradability, biocompatibility, scalability, and sustainability^{119, 120}. The size of the nanoparticles plays a crucial role in various transport process rates, affecting for example specificity in binding or adhesion and reactivity^{116, 121}. Nanotechnology-based drug delivery systems can be categorized according to the route of administration into oral delivery, transdermal delivery, injectable delivery, topical delivery, nasal/pulmonary delivery, and implantable delivery^{15, 119, 120}. These diverse delivery routes allow for tailored approaches to meet specific therapeutic needs and improve treatment efficacy. Below, we review the major delivery categories.

4.1. Targeted drug delivery

Targeted drug delivery refers to the ability of nanoparticles to reach specific cells or organs following systemic administration (e.g., intravenous infusion). Electrosprayed nanoparticles have been extensively investigated for targeted drug delivery applications, since these particles can be engineered to deliver drugs to specific sites in the body, improving drug bioavailability and reducing systemic side effects^{122, 123}. This targeting is achieved by functionalizing the particles with targeting ligands or surface modifications to enhance their affinity for specific cells or tissues, enabling precise drug delivery¹²². Such targeted nanoparticles have shown promise in various therapeutic areas, including cancer, cardiovascular disorders, and neurological conditions^{124, 125}. Although some targeting may occur passively through enhanced permeability and retention (EPR) effects, surface modifications play a crucial role in actively targeting specific cells or tissues. Overall, electrosprayed nanoparticles represent a promising avenue for targeted drug delivery, offering enhanced solubility, stability, and bioavailability, as well as enabling combination therapy approaches. Ankireddy et al synthesized and characterized the electrospray acetyl curcumin-loaded core/shell liposome nanoparticles for drug delivery and theranostic applications. By using electrospray nanoparticles, they could obtain a uniform nan-size liposome nanoparticles (LNPs). The prepared LNPs release the drug in sustained maximum release of the drug (48.5%) for the period of 4 days ¹²⁶ (Fig 4). Further, Reza et al, Electrosprayed nanoparticles encapsulating berberine within a PLA matrix via coaxial electrospray have been developed for sustained drug release, targeting specific therapeutic applications such as anticancer activity¹²⁷(Fig 3). Shi Xu et al, They prepared coaxial core-shell nanoparticles loaded with gemcitabine for targeted drug delivery to tumors, utilizing folate-chitosan for tumor targeting. They showed that prepared core shell nanoparticle are having high uptake efficiency for pancreatic cancer¹²⁸. Moreover, electrosprayed chitosan nanoparticles loaded with curcumin have demonstrated enhanced bioavailability and potent anticancer activity in both in vitro and in vivo studies¹²⁹. Nanoparticles have also been utilized for combination therapy by loading multiple drugs. Paclitaxel-loaded PLGA nanoparticles prepared through electrospraying exhibited improved inhibition of tumor growth in a breast cancer animal model^{130, 131}. This PLGA nanoparticle can employed by active targeting or by passive targeting through EPR.Similarly, electrosprayed doxorubicin-loaded hydrogel microparticles showed improved drug release and cytotoxicity for tumor therapy¹³². The enhanced chemotherapy efficacy occur through passive targeting by EPR effect.

Figure 4: -.

Illustration depicting the synthesis and characterization of acetyl curcumin-loaded core/shell liposome nanoparticles via an electrospray process for drug delivery and theranostic applications¹²⁶.

Figure 3: -.

Schematic representation illustrating the fabrication, characterization, and optimization processes of berberine-loaded PLA nanoparticles using coaxial electrospray for sustained drug release¹²⁷.

Furthermore, electrospray techniques have been utilized to fabricate nanoparticles loaded with drugs such as doxorubicin, brimonidine tartrate, and cyclophosphamide, aiming to improve drug bioavailability and prolong residence time^133–135. The electrospray deposition system has also been employed to synthesize nanoparticles for controlled release of anticancer drugs¹³⁵. Moreover, electrospraying has been used to create stimuli-responsive drug particles and peptide-based particulates for drug encapsulation¹³⁶. Thus, the electrosprayed nanoparticles exhibit significant potential for targeted drug delivery, improving drug solubility, stability, and bioavailability, while also enabling combination therapy approaches. Table 3 contains information about Electrosprayed nanoparticles for Drug Delivery: Delivery Type, Loaded Compounds, and Therapeutic Applications. And Table 4 described the Patents Related to Electrospray and Nanoparticle Technologies for various applications.

Table 3:-.

Electrosprayed nanoparticles for Drug Delivery: Delivery Type, Loaded Compounds, and Therapeutic Applications

Drug Delivery Type	Drug/Loaded Compound	Raw material/Nanoparticle Type	Biomedical Application	Reference
Targeted Drug Delivery	Paclitaxel	PLGA nanoparticles	Breast Cancer	130
	Doxorubicin	Chitosan nanoparticles	Cancer	132
	Doxorubicin	Chitosan nanoparticles	Breast and Colon Cancer	137
Topical Drug Delivery	Lidocaine	Solid lipid nanoparticles	Analgesic Therapy	138
	Ketoconazole	Solid lipid nanoparticles	Antifungal	139
	Tretinoin	Solid lipid nanoparticles	Treat Acne	140
	Clotrimazole	Solid lipid nanoparticles	Fungal Keratitis	141
	Ciprofloxacin	Eudragit RS100 nanoparticles	Antimicrobial	142
	Terbinafine	Chitosan nanoparticles	Fungal	143
	Tretinoin	PLGA nanoparticles	Thrombotic Diseases	144
	Ibuprofen	PLGA nanoparticles	Anti-inflammatory	145
	Methotrexate	PLGA Nanoparticles	Cancer	146
	Retinoic acid	Retinoid prodrug	Cancer	147
	Azithromycin	Eudragit L100 Nanoparticles	Ocular infection	148
	Nifedipine	Chitosan-PlGA Nanoparticles	Plumonary Fibrosis	149
	Silver sulfadiazine	Silver Nanoparticles	Deep Burns	150
	Acyclovir	Perflluoroalkyl Alpha-cyclodextrine	Herpes virus	151
Injectable Drug Delivery	Insulin	Chitosan nanoparticles	Diabetes	152
	Methotrexate	PLGA nanoparticles	Cancer	153
	Paclitaxel	PLGA nanoparticles; lipid nanoparticles	Cervical Cancer	154, 155
	Imatinib	PLGA nanoparticles	Cervical Cancer	156
	Chalcone (KAZ3)	Mesoporous particles	Cancer	157
	Brimonidine tartrate	Chitosan Nanoparticles	Glaucoma	158
	Cyclophosphamide	Gliadin	Anti-Cancer	135
	Doxorubicin	Lipoplex Nanoparticles	Myeloid Leukemia	159
Oral Drug Delivery	Insulin	Chitosan nanoparticles	Diabetes	160
	Curcumin	Chitosan nanoparticles	Cancer	129
	Naproxen	Eudragit nanoparticles	Anti-inflammatory	161

Table 4:-.

Patents Related to Electrospray and Nanoparticle Technologies

Sr. No	Patent title	Application	Patent Application Number
1	Nanoparticle coating of surfaces (2019)	For controlled drug release	US-10252289-B2162
2	Device with electrospray coating to deliver active ingredients (2017)	To deliver one or more Active ingredient for medical treatment	US-9642694-B2163
3	Drug-loaded albumin microparticle or nanoparticle and preparation method thereof (2022)	For encapsulation of drug in albumin nanoparticle for biomedical use	CN-109453138B164
4	Method And Apparatus For AC Electrospray (2012)	Invention may be used to generate aerosol drops for respiratory drug delivery or as a microencapsulation technique for the encapsulation of drugs, DNA, protein, osteogenic or dermatological, etc.	US 8267914 B1165
5	Method for preparing polymer electrosprays (2005)	producing stable polymer electrosprays of water-soluble polymers and Water-insoluble polymers using one or more solvents having high dielectric constants	EP-535949 A1166
6	High Mass Throughput Particle Generation Using Multiple Nozzle Spraying (2015)	multiple nozzle structures for producing multiple sprays of particles, e.g., nanoparticles, for various applications, e.g., pharmaceuticals	US-9050611 B2167
7	Electrospray employing corona assisted cone-jet mode (1999)	For the production of Ultra fine aerosol particle uniformly	US5873523A168
8	Preparation method for gliadin nanoparticles by electrospray (2013)	For drug delivery application	KR101390212B1169
9	Apparatus and method for electrostatic spray coating of medical devices(2007)	method are used for electrostatic spray deposition of coatings onto small medical devices, such as stents	US7556842B2170

4.2. Topical drug delivery:

Electrosprayed nanoparticles have also emerged as a promising drug delivery system for topical applications, offering various advantages such as controlled release, enhanced bioavailability, improved skin penetration, sustained release, and versatile formulations^{15, 119, 131, 171}. For instance, Usharani Nagarajan et al. prepared a collagen solid nanoparticle using one- step electrospray deposition method. Collagen play a major role in formation of structure and function of skin, cartilage, bone etc. Initially they observed the nanofibers were formed so, to make the nanoparticles they increased the conductivity of solution by addition of salts. They added a theophylline as drug model into the nanoparticle by coaxial spray technique¹⁷². Recently, Bahareh Azimi et al., they combine the electrospinning and electrospray technique to build a dual drug-loaded nanoparticle and ultrafine nanofibers. Basically, they to prepared nanofibers using PHBHV (poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in that they loaded dexamethasone. And in PLGA (poly(lactic-co-glycolic acid) in they added rhodamine as second drug molecule. To developed they patch they used roller collector, at one side they spray the PLGA-Rhodamine and other PHBHV-dexamethasone polymer solution simultaneously. This prepared patch release the drug for over 4 week in a sustained manner¹⁷³(Fig 5). Mansoor Mandegari et al., prepared a nanoparticle for treatment of acne using electrospray method. To prepare this nanoparticle they used PVA (Polyvinyl alcohol) and clindamycin as which commonly used for treating acne. These nanoparticles were sprayed on cotton for easy application to release the drug for longer duration¹⁷⁴. Cui et al. used electrospray to prepare clotrimazole-loaded micro/nanoparticles for topical delivery for treatment of fungal keratitis¹⁷⁵. Similarly, Dillen et al. developed electrosprayed Eudragit RS100 nanoparticles loaded with ciprofloxacin, an anti-microbial agent used for the treatment of skin and soft tissue infections¹⁴². Chatterjee et al. loaded methotrexate into PLGA nanoparticles, resulting in improved stability and skin penetration, while Adibkia et al fabricated and characterized nanoparticles of MDF-ERS by using electrospray deposition method^{146, 153}.

Figure 5:-.

Examples of the versatility of electrospray/electrospinning system with different drug/PLGA NPs produced via electrospray, also in combination with electrospun fiber meshes: (A) schematic of the used process; (B) Ciprofloxacin-loaded PLGA NPs (~200 nm), electrosprayed for a short time (50,000× magnification; 10 kV; scale bar 2 μm); (C) Tetracycline hydrochloride (HCl)-loaded PLGA NPs (5000× magnification; 10 kV; scale bar 20 μm); (D) RHO-loaded PLGA NPs deposited onto PEOT-PBT electrospun fibers (10,000× magnification; 10 kV; scale bar is 10 μm); lens (40,000× magnification; 10 kV; scale bar is 3 μm)¹⁷³.

In these studies, electrosprayed nanoparticles loaded with the respective drugs exhibited improved stability, skin penetration, antibacterial activity, antifungal activity, and antiviral activity. Moreover, electrosprayed nanoparticles have been utilized for wound dressing applications¹⁷⁶, demonstrating enhanced antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Additionally, Levana et al. developed an antibacterial surface by efficiently depositing silica homogeneously onto polyethylene terephthalate (PET) film to achieve hydrophobic and anti-adhesive properties inhibiting bacterial adhesion using both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria¹⁷⁷. Xiaoming Cui et al. developed hydrodynamic nanoparticles for the treatment of fungal keratitis using two drugs: natamycin (NAT) and clotrimazole (CLZ). To load these drugs into the nanoparticle system, they utilized a co-axial electrospinning technique. The outer layer of the nanoparticles was composed of PLGA, while the inner layer consisted of chitosan. CLZ was combined with PLGA in acetone, and NAT was incorporated with chitosan in 1% acetic acid. This formulation exhibited sustained drug release over a period of 36 hours. Furthermore, both in vivo in and in vitro studies confirmed that the formulation was safe and effective against C. albicans, demonstrating potent antifungal activity¹⁴¹ (Fig 6).

Figure 6:-.

Integrated schematic illustrating the preparation and function of NAT/CLZ@CTS/PLGA nanoparticles (NPs) (A). Along with antifungal activities against C. albicans (B). Additionally, the figure presents results from ophthalmic irritation studies (C) and local allergenic tests (C). Ocular observation during a 12-hour treatment with PBS, NAT/CLZ solution, and NAT/CLZ@CTS/PLGA NP formulations. Histological analysis (H&E stain) of rat eyes treated with different formulations, showing the corneal epithelium, anterior limiting layer and corneal stroma with a scale bar of 50 μm. (D) Skin observation and histology analysis (H&E stain) of exposed skin areas excised at 72 hours, displaying the stratum corneum (SC), epidermis, and dermis with a scale bar of 50 μm”¹⁴¹.

4.3. Injectable drug delivery

These injectable micro/nanoparticles find application in diverse medical contexts, including intertumoral injection (where localized and sustained drug release in the tumour tissue enhances anticancer efficacy)¹⁷⁸, periodontal injection, intraperitoneal injection, subcutaneous injection, and more. Extensive research has been conducted in the field of cardiomyoplasty (a surgical procedure that uses healthy muscle from another part of the body to support a failing heart), demonstrating the promising potential of injectable nanoparticles^{14, 179, 180}. Injections are a frequent route of parenteral delivery because they are intended to reduce the likelihood of systemic side effects and harmful effects on healthy cells and tissues¹⁸¹. The strict quality standards for injections go above and beyond the fundamental demand that they be pyrogen-free. Injection quality is greatly influenced by elements including liquid stability, uniformity of injectable particles, and appropriateness of particle size. Therefore, improving the particle size and dispersibility of injectable micro/nanoparticles is becoming increasingly important. In this context, electrospray (ES) technology offers a number of benefits due to its capacity to precisely control particle size, guarantee homogenous particles, permit maximum drug loading, and preserve stability⁹. As a result, it has quickly gained popularity in the manufacture of injectable micro/nanoparticles. Electrospray methods combined with the use of aseptic procedures allow for the creation of pyrogen-free micro/nanoparticles that satisfy injection criteria. Notably, high drug loading capacity electrosprayed micro/nanoparticles can be injected into the body to create a drug reservoir. This reservoir allows for gradual, regulated drug release over time, lowering injection frequency while increasing therapeutic efficacy^{182, 183}. Additionally, there are numerous uses for drug-loaded micro- and nanoparticles made using electrospray technique. They can be injected straight into the body or added to hydrogels that have characteristics like pH sensitivity and temperature sensitivity. Their targeting and sticky powers are strengthened by their adaptability. For instance, Trinh et al. (2020) developed injectable pH–temperature sensitive chitosan nanoparticles for insulin delivery, showcasing improved stability and efficacy. They developed a composite using chitosan-insulin electrospray nanospheres and oligomer serine-b-poly(lactide)-b-poly(ethylene glycol)-b-poly(lactide)-b-oligomer serine (OS-PLA-PEG-PLA-OS) Penta block copolymer as the matrix. It was discovered that the chitosan-insulin nanoparticles had been harmoniously incorporated into the matrix. Due to the hydrogel’s slower disintegration, the delayed release of insulin was increased. It was discovered that the streptozotocin-induced diabetic model’s blood glucose level-lowering effect persisted more than 60 hours after injection¹⁵².Ali Akbar Karimi Zarchi et al, prepared N-Acetylcyteine loaded nanoparticle by electrospray technique. They study the various parameter, of electrospin like concentration, flow rate, distance between the collector and needle. They prepared the nanoparticles at flow rate of 0.06(ml/h), polymer concentration 0.5(%w/w) and distance were 9.28(cm). At this parameter the size of particle was 122(nm). They drug loading 5% and encapsulation efficiency for 54.5%¹⁸⁴. Further, Yue Zhang et al, developed a multidrug release nanocarriers using coaxial electrospray method for type diabetes. They laoded two drugs saxagliptin and dapagliflozin in PLGA polymer. They preapred particles size was in range of 534.8 to 708.6 nm. And they could achived the 90% encapsulation of drugs. This indicate that multiple drug can be loaded coaxial method using PLGA polymer for sustained and controlled release¹⁸⁵. Khare et al. (2021) created electrosprayed lipid nanoparticles for siRNA delivery, while Swetledge et al. (2021) formulated polymeric nanoparticles for ocular drug delivery, resulting in improved cellular uptake, gene silencing, bioavailability, and sustained release^{186, 187}. Furthermore, numerous studies have explored the use of electrosprayed formulations to improve the delivery of drugs such as paclitaxel, doxorubicin, methotrexate, gemcitabine, camptothecin, docetaxel, cisplatin, and etoposide^{156, 157, 188–193}. Other approaches, such as PLGA porous beads as microscaffolds¹⁹⁴ and oxygen release systems¹⁰⁷, have also been investigated for cardiomyoplasty. Injectable hydrogels combining drug-loaded alginate microspheres with PLGA-PEG-PLGA hydrogels have also been developed¹⁹⁵.

4.4. Oral drug delivery

Electrosprayed nanoparticles have shown promise in enhancing the oral delivery and bioavailability of drugs with poor solubility or low oral bioavailability¹⁵³. For example, curcumin is widely used for biomedical applications such as anticancer or antimicrobial therapies. But some of its limitations are the poor water solubility, poor bioavailability and rapid degradation under alkaline pH. To overcome these limitations Baspinar et al. developed electrosprayed zein-chitosan nanoparticles loaded with curcumin and piperine, to enhanced the solubility and bioavailability of curcumin¹²⁹(Fig 7). They could achieve encapsulation efficiency of 89% for curcumin and 87% for piperine. Further by cytotoxicity assay they observed that at 10-25ug/ml of curcumin could able to reduce almost 50% of neuroblastoma cells¹²⁹. Several other studies have explored the potential of nanoparticle formulations for oral drug delivery. Rodríguez‐Félix, et al. focused on electrosprayed zein nanocarriers for the oral delivery of quercetin to increase its bioavailability. Quercetin is a hydrophobic flavonoid that possesses high antioxidant activity, and therefore has low oral bioavailability. They observed encapsulation efficiency was very high 87.9 to 93%. And in vitro bioavailability was much higher for trapped quercetin (5.9%) compared to free quercetin which was (1.9%) than of Gastrointestinal tract (GIT) digestion¹⁹⁶. Yang et al. developed silymarin-loaded nanoparticles for oral delivery for hepatic protection, Yousaf et al. prepared electrosprayed fenofibrate-loaded nanoparticles is to enhance the aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate. Fenofibrate is a drug used to lower cholesterol and triglycerides in the blood, but its poor water solubility limits its effectiveness when administered orally, and Tang et al. investigated electrosprayed catechin-loaded nanoparticles for oral delivery for application antioxidant and anti-inflammatory properties, among other potential health-promoting effects. ^197–199.

Figure 7:-.

A:- Schematic presentation of the core and shell electrospray apparatus and The core shell model of the curcumin and piperine loaded zein-chitosan nanoparticles. B:- SEM images of curcumin and piperine loaded zein-chitosan nanoparticles with varying ratios of piperine solution to chitosan solution from 1:10 to 1:50 (A: CPZChN1, B: CPZChN2, C: CPZChN3, D: CPZChN4, E: CPZChN5, F: CPZChN6, G: CPZChN7, H: CPZChN8, I: CPZChN9).C:- The final curcumin and piperine loaded zein-chitosan nanoparticle product dispersed in a mixture of glycerol (19%, w/w) and water and as powder filled in capsules¹²⁹.

These studies collectively demonstrate the potential of nanoparticle formulations in improving drug delivery, enhancing bioavailability, and achieving therapeutic efficacy for various drugs. Table 2 provides a general overview of nanoparticles used for various drugs/compounds in biomedical applications. These nanotechnology-based approaches hold promise for overcoming the limitations of conventional oral drug delivery methods.

5. Drawback of electrospin method

While electrospinning offers numerous advantages for preparing nanoparticles, it also comes with several drawbacks. One significant concern is the necessity of using solvents such as chloroform, methanol, and ethanol. These solvents can be toxic to the environment and pose risks for biomedical applications due to potential residue even after drying. The use of solvents further limits the incorporation of biological materials such as proteins, antibodies, and cells, as these solvents can alter or damage their biological properties. This limitation poses a significant hurdle for applications that require the integration of biological materials Moreover, the process of making nanoparticles using electrospinning is time-consuming, and scaling up production for industrial applications presents considerable challenges. Although some scientists have tried using multiple nozzles to increase production, this approach demands additional instruments and equipment, complicating the setup. Setting up electrospinning equipment itself is no small feat. It requires a large space, high voltage supplies, and a controlled environment to maintain proper humidity and air quality. Ensuring the safety of personnel also demands regular training and safety checks. Another major drawback is that not all polymers are suitable for formulating nanoparticles through electrospinning. The process requires polymers with specific molecular weights, compatibility with other polymers, and solubility in solvents with lower evaporation temperatures. Finding the right combination of polymers often involves a lot of trial and error to achieve the desired size and uniformity of nanoparticles, given the many parameters that influence their formation. Despite these challenges, electrospinning remains a valuable method for nanoparticle production, and ongoing research continues to address these issues to improve its feasibility and safety for broader applications.

6. Conclusion and Future Perspective

We provide a comprehensive review of the application of the electrospraying technique for nanoparticle production, highlighting its principles, particle characteristics, and the influence of different process parameters on nanoparticle morphology. Further, we reviewed the significant potential of the electrospray nanoparticle technology for a wide range of biomedical applications, particularly in drug delivery. The electrosprayed nanoparticles possess unique properties which have advantages over traditional techniques, and is more efficient in the use of chemicals, reduced labour, allows high drug loading and loading of multiple drugs in one step. Furthermore, monodisperse nanoparticles are formed without requiring complex instruments, and production is scalable, making them suitable for various administration routes and therapeutic needs.

The potential for personalized medicine is also significant, as electrosprayed nanoparticles can encapsulate drugs tailored to an individual patient’s genetic makeup, disease condition, and drug response. This personalized approach enhances drug efficacy while minimizing adverse effects, ultimately improving patient outcomes. Additionally, these nanoparticles can be utilized for disease diagnosis by encapsulating contrast agents or diagnostic agents, allowing for precise delivery to specific tissues or cells and enhancing the accuracy of diagnosis. Furthermore, the development of multifunctional nanoparticles with diverse therapeutic functionalities, achieved through the modification of nanoparticles with various functional groups, opens new possibilities for targeted delivery, and controlled drug release. For successful translation to clinical applications, further research is necessary to assess the safety and efficacy of electrosprayed nanoparticles in human subjects through clinical trials. Optimizing the design and formulation of these nanoparticles will be crucial to ensure their effectiveness and scalability. Additionally, incorporating theranostic agents into electrosprayed nanoparticles, such as imaging agents or biosensors, can enable simultaneous diagnostic and therapeutic functions, allowing for monitoring of drug delivery, drug efficacy, and disease progression. Electrospray nanoparticles have emerged as a highly promising technology for biomedical drug delivery applications, offering numerous future perspectives for advancement.

In conclusion, electrospraying holds great promise in biomedical applications, providing a versatile and effective platform for targeted drug delivery and other therapeutic interventions. Continued research and development in this field are expected to lead to further advancements and the translation of these technologies into clinical practice, benefiting patients and improving treatment outcomes.

Figure 2: -.

Schematic representation of deposition of electrosprayed nanoparticles⁶⁴.

ABBREVIATIONS

EHDA

Electrohydrodynamic atomization

PEG

Polyethylene glycol

PCL

Polycaprolactone

PVA

Poly (vinyl alcohol)

LNP

Liposome nanoparticles

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no new data were created or analyzed in this study.