Table 2.

Expertise gained in nanomedicine approaches for pulmonary infections.

Product/Formulation type	Indication	Therapeutic observations	Comments
Lipoquin®	Local antibiotic treatment for lung infections	Ciprofloxacin unilamellar nano liposome nebulized delivery system provides the reduction of dose frequency to a once daily treatment while maintaining a high local concentration in clinical evaluations compared to larger size liposomes [122].	Commercial nano liposomal products for lung delivery are intended to increase the permeation, intra cellular drug enhancement for pulmonary infections, and these approaches provide insights for future therapeutics targeting systems with enhanced therapeutic response to fight pulmonary infections.
Arikayce® (liposomal Amikacin)	Non-tuberculous Mycobacterial Lung Disease	Liposomal Amikacin system is shown to increase intracellular drug concentration and overall therapeutic improvement [123], [191].
Ambisome® (liposomal amphotericin B)	Allergic bronchopulmonary aspergillosis	Currently in phase 2 clinical trials for Allergic Bronchopulmonary Aspergillosis treatment (ClinicalTrials.gov Identifier: NCT02273661).
Liposomal amikacin for inhalation (LAI)	Bronchiectasis (Phase II clinical trial)	LAI produces improvement in sputum conversion with limited systemic toxicity in patients with refractory MAC (Mycobacterium avium complex) disease [124].	Strategies with liposomal based nano or emulsified systems had high lung mucosa penetration capabilities. These strategies help in drug deposition with high retention in airways; these investigations provide clues for future COVID-19 like pulmonary infection associated drug delivery applications.
Tobramycin nano lipid carriers (NLCs)	P. aeruginosa infections associated with cystic fibrosis	Drug NLCs combat P. aeruginosa infection and also increase in vivo mucus penetration [192].
pGM169 drug with GL67A lipid solution	Cystic fibrosis (Phase IIb clinical trial)	Increased drug deposition and retention in the proximal airways [193].
MERS‐CoV S‐containing nanoparticles	Recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination as a vaccine	MERS-CoV S nanoparticle vaccine produced high titter anti-S neutralizing antibody and protected mice from MERS-CoV infection in vivo [125].	Introduction of vaccinated with MERS-CoV S nanoparticles developed a MERS-CoV neutralizing antibody response targeted to MERS-CoV S.
Immunoprophylactic strategy with protein cage nanoparticle (PCN)	Pulmonary viral infections including influenza viruses, a mouse-adapted SARS-coronavirus	Pulmonary instillation of PCN dramatically enhanced the subsequent host immune responses to primary viral infections of the lungs [126].	Like liposomal strategies, polymeric nano systems also enhance localization of drug in the lung regions for a better therapeutic response.
PS-341 loaded PLGA-PEG NPs	Cystic fibrosis (Preclinical study in mice)	Enhanced drug localization with NPs to the lungs, helps in reducing immunosuppressive side effects resulting from PS-341 systemic administration over 11 days [127].
PRINT® (Particle Replication in Non-wetting Templates) technology	Influenza vaccine	To deliver influenza vaccine antigens, poly (lactide-co-glycolide) PRINT particles were designed to bind to a commercial trivalent injectable influenza vaccine electrostatically [194].	Increased understanding of the delivery of the vaccine antigen. This approach has increased vaccine effectiveness and reduces the amount of antigen necessary to induce an immune response.
Gold nanorod-based heptad repeat (HR1) peptide inhibitor	Middle East respiratory syndrome coronavirus (MERS-CoV)	Pregnancy-induced hypertension (PIH), is a potent HR1 inhibitor and can selectively inhibit MERS-CoV S with an IC50 value of 1.171 μM. The developed pregnancy-induced hypertension (PIH) gold nanorods (PIH-AuNRs) exhibited a 10-fold higher inhibitory activity than PIH and can completely inhibit cell fusion at 1.171 μM with good biostability, excellent targeting ability and minimum off target effects. Therefore, PIH-AuNRs are a promising antiviral agent and may have a huge impact on developing pharmaceuticals in the clinic [119].	HR1 peptide inhibitors have been developed to inhibit HR1/HR2-mediated membrane fusion between MERS-CoV and host cells, which is the major pathway of MERS-CoV-induced host infections.
Virus like nanoparticles (VLPs)	Enhancing or triggering the strong immune response in pulmonary infections	Virus mimicking empty particulate structures [128], [129].	Hollow virus like particulate structures which lack in genetic material will provoke or enhance a strong immune response to combat lung associated infections.