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Review Article

Liposomal drug delivery to the lungs: a post covid-19 scenario

, &
Pages 410-424 | Received 27 Oct 2022, Accepted 10 Mar 2023, Published online: 19 Apr 2023

References

  • Abdellatif, A.A.H., et al., 2021. Recent updates in COVID-19 with emphasis on inhalation therapeutics: Nanostructured and targeting systems. Journal of drug delivery science and technology, 63, 102435.
  • Abdelrady, H., et al., 2019. Exploiting gelatin nanocarriers in the pulmonary delivery of methotrexate for lung cancer therapy. European journal of pharmaceutical sciences, 133, 115–126.
  • ACTEMRA 2008. Highlights of prescribing information.
  • Adorni, G., et al., 2019. Aerosolization performance of jet nebulizers and biopharmaceutical aspects. Pharmaceutics, 11 (8), 406.
  • Alavi, M., Asare-Addo, K., and Nokhodchi, A., 2020. Lectin protein as a promising component to functionalize micelles, liposomes and lipid NPS against coronavirus. Biomedicines, 8 (12), 580.
  • Alavi, S.E., et al., 2022. PEG-grafted liposomes for enhanced antibacterial and antibiotic activities: an in vivo study. NanoImpact, 25, 100384.
  • Ali, M., 2010. Pulmonary drug delivery: Handbook of Non-Invasive Drug Delivery Systems. Oxford, England: William Andrew, 209–246.
  • Ali, Z.A., and El-Mallakh, R.S., 2020. Nebulized lidocaine in COVID-19, an hypothesis. Medical hypotheses, 144, 109947.
  • Alipour, S., Mahmoudi, L., and Ahmadi, F., 2023. Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19. Drug delivery and translational research, 13 (3), 705–715.
  • Amararathna, M., et al., 2019. Pulmonary nano-drug delivery systems for lung cancer: current knowledge and prospects. Journal of lung health and diseases, 3 (2), 11–28.
  • Ameratunga, R., et al., 2020. Inhaled modified angiotensin converting enzyme 2 (ACE2) as a decoy to mitigate SARS-CoV-2 infection. The New Zealand medical journal, 133 (1515), 112–118.
  • Anderson, M.J., Parks, P.J., and Peterson, M.L., 2013. A mucosal model to study microbial biofilm development and anti-biofilm therapeutics. Journal of microbiological methods, 92 (2), 201–208.
  • Arber Raviv, S., et al., 2022. Lung targeted liposomes for treating ARDS. Journal of controlled release, 346, 421–433.
  • Banaschewski, B., and Hofmann, T., 2019. Inhaled antibiotics for mycobacterial lung disease. Pharmaceutics, 11 (7), 352.
  • Boisvert, A.A., et al., 2016. Microbial biofilms in pulmonary and critical care diseases. Annals of the American Thoracic Society, 13 (9), 1615–1623.
  • Bošnjak, B., et al., 2021. Intranasal delivery of MVA vector vaccine induces effective pulmonary immunity against SARS-CoV-2 in rodents. Frontiers in immunology, 12, 772240.
  • Cai, X., et al., 2016. Preparation, characterization and pulmonary pharmacokinetics of a new inhalable zanamivir dry powder. Drug delivery, 23 (6), 1962–1971.
  • Caly, L., et al., 2020. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral research, 178, 104787.
  • Carpagnano, G.E., et al., 2014. Aspergillus spp. colonization in exhaled breath condensate of lung cancer patients from Puglia Region of Italy. BMC pulmonary medicine, 14 (1), 22.
  • Cascella, M., et al., 2020. Features, Evaluation and Treatment Coronavirus (COVID-19). Treasure Island: NCBI Bookshelf.
  • Chen, N., et al., 2020. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 395 (10223), 507–513.
  • Cipolla, D., Blanchard, J., and Gonda, I., 2016. Development of liposomal ciprofloxacin to treat lung infections. Pharmaceutics, 8 (1), 6.
  • Cipolla, D., et al., 2014. Development and characterization of an in vitro release assay for liposomal ciprofloxacin for inhalation. Journal of pharmaceutical sciences, 103 (1), 314–327.
  • DailyMed. 2022. TOBI- tobramycin solution. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=94f9e516-6bf6-4e30-8dde-8833c25c2560.
  • Daltro, P., et al., 2011. Pulmonary infections. Pediatric radiology, 41 (S1), 69–82.
  • Dasaraju, P.V., Liu, C., and Baron, S., 1996. Chapter 93, infections of the respiratory system. In: Medical microbiology. Alveston, TX.
  • Derbali, R.M., et al., 2019. Tailored nanocarriers for the pulmonary delivery of levofloxacin against pseudomonas aeruginosa: a comparative study. Molecular pharmaceutics, 16 (5), 1906–1916.
  • Deshpande, D., et al., 2002. Aerosolization of lipoplexes using AERx pulmonary delivery system. AAPS pharmascience, 4 (3), 12–21.
  • Dhanani, J.A., et al., 2019. Lung pharmacokinetics of tobramycin by intravenous and nebulized dosing in a mechanically ventilated healthy ovine model. Anesthesiology, 131 (2), 344–355.
  • Djukanović, R., et al., 2014. The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial. American journal of respiratory and critical care medicine, 190 (2), 145–154.
  • Dong, C., et al., 2021. Intranasal vaccination with influenza HA/GO-PEI nanoparticles provides immune protection against homo- and heterologous strains. Proceedings of the national academy of sciences, 118 (19), e2024998118.
  • Douglas, A., 2021. A study of intranasal ChAdOx1 nCOV-19. https://clinicaltrials.gov/ct2/show/NCT04816019.
  • Duddu, P., 2020. Coronavirus outbreak: top coronavirus drugs and vaccines in development. https://www.clinicaltrialsarena.com/analysis/coronavirus-mers-cov-drugs/.
  • Edwards, D.A., et al., 1997. Large porous particles for pulmonary drug delivery. Science, 276 (5320), 1868–1871.
  • Eedara, B.B., et al., 2021. Inhalation delivery for the treatment and prevention of COVID-19 infection. Pharmaceutics, 13 (7), 1077.
  • Effros, R.M., and Mason, G.R., 1983. Measurements of pulmonary epithelial permeability in vivo. American review of respiratory disease, 127, S59–S65.
  • Ehsan, Z., and Clancy, J.P., 2015. Management of Pseudomonas aeruginosa infection in cystic fibrosis patients using inhaled antibiotics with a focus on nebulized liposomal amikacin. Future microbiology, 10 (12), 1901–1912.
  • Elhissi, A.M.A.,et al., 2014. New delivery systems - liposomes for pulmonary delivery of antibacterial drugs. In: Novel Antimicrobial Agents and Strategies. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 387–406.
  • EMA, 2009. Requirements for clinical documentation for orally inhaled products including requirements for demonstration of therapeutic equivalence between 2 inhaled products for use in treatment of asthma & chronic obstructive pulmonary disease -Scientific guideline [online]. European Medicines Agency. Available from: https://www.ema.europa.eu/en/requirements-clinical-documentation-orally-inhaled-products-including-requirements-demonstration
  • Enenkel, S., and Stille, W., 1988. Infections of the respiratory tract. In: Antibiotics in the tropics. Berlin Heidelberg: Springer, 105–141.
  • Erickson, E.N., Bhakta, R.T., and Mendez, M.D., 2021. Pediatric Bronchiolitis. StatPearls Publishing, Treasure Island.
  • European Medicines Agency: an unacceptable choice, 2011. Prescrire international, 20 (121), 278.
  • Evans, P.L., and Mungcal, J., 2010. Albuterol sulfate inhalation aerosol. Journal of asthma & allergy educators, 1 (2), 75–76.
  • Fan, X., et al., 2021. Intrapulmonary vaccination induces long-lasting and effective pulmonary immunity against Staphylococcus aureus pneumonia. The journal of infectious diseases, 224 (5), 903–913.
  • FDA and CDER. 2015. Levalbuterol tartrate inhalation aerosol metered. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_021730.pdf
  • Fodor, K., and Tóth, A., 2009. Handbook of pulmonary diseases : etiology, diagnosis and treatment. Nova Biomedical Books, 337. ISBN-10:1607418983; ISBN-13:9781607418986; Pub. Date:10/01/2009.
  • Folkesson, H.G., Weström, B.R., and Karlsson, B.W., 1990. Permeability of the respiratory tract to different-sized macromolecules after intratracheal instillation in young and adult rats. Acta physiologica scandinavica, 139 (2), 347–354.
  • Fontana, M.C., et al., 2014. Polymeric controlled release inhalable powder produced by vibrational spray-drying: one-step preparation and in vitro lung deposition. Powder technology, 258, 49–59.
  • Ganesan, S., Comstock, A.T., and Sajjan, U.S., 2013. Barrier function of airway tract epithelium. Tissue barriers, 1 (4), e24997.
  • García-Montero, C., et al., 2021. An updated review of sars-cov-2 vaccines and the importance of effective vaccination programs in pandemic times. Vaccines, 9 (5), 433.
  • Garg, T., et al., 2016. Spray-dried particles as pulmonary delivery system of anti-tubercular drugs: design, optimization, in vitro and in vivo evaluation. Pharmaceutical development and technology, 21 (8), 951–960.
  • Geller, D.E., et al., 2002. Pharmacokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis. Chest, 122 (1), 219–226.
  • Gregoriadis, G., 2021. Liposomes and mRNA: two technologies together create a COVID-19 vaccine. Medicine in drug discovery, 12, 100104.
  • Gupta, P.V., Nirwane, A.M., and Nagarsenker, M.S., 2018. Inhalable levofloxacin liposomes complemented with lysozyme for treatment of pulmonary infection in rats: effective antimicrobial and antibiofilm strategy. AAPS PharmSciTech, 19 (3), 1454–1467.
  • Hastedt, J.E., et al., 2016. Scope and relevance of a pulmonary biopharmaceutical classification system AAPS/FDA/USP Workshop March 16–-17th, 2015 in Baltimore, MD. AAPS open, 2 (1), 1–20.
  • Hava, D.L., 2016. Advances in pulmonary delivery of inhaled anti-infectives. ONdrugDelivery, 2016 (66), 14–19.
  • He, S., et al., 2022. A roadmap to pulmonary delivery strategies for the treatment of infectious lung diseases. Journal of nanobiotechnology, 20 (1), 101.
  • Helen Fitton, J., et al., 2020. Fucoidan and lung function: value in viral infection. Marine drugs, 19 (1), 4.
  • Ho, D.K., et al., 2018. Polysaccharide submicrocarrier for improved pulmonary delivery of poorly soluble anti-infective ciprofloxacin: preparation, characterization, and influence of size on cellular uptake. Molecular pharmaceutics, 15 (3), 1081–1096.
  • Ho, D.K., et al., 2019. Challenges and strategies in drug delivery systems for treatment of pulmonary infections. European journal of pharmaceutics and biopharmaceutics, 144, 110–124.
  • Huang, Z., et al., 2021. Nanoparticle-mediated pulmonary drug delivery: state of the art towards efficient treatment of recalcitrant respiratory tract bacterial infections. Drug delivery and translational research, 11 (4), 1634–1654.
  • Hwang, S.S., et al., 2020. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 367 (6483), 1255–1260.
  • Ibrahim, M., Verma, R., and Garcia-Contreras, L., 2015. Inhalation drug delivery devices: technology update. Medical devices, 8, 131–139.
  • Iwabuchi, K., et al., 2020. Therapeutic potential of ciclesonide inhalation for COVID-19 pneumonia: report of three cases. Journal of infection and chemotherapy, 26 (6), 625–632.
  • Japiassu, K.B., et al., 2022. Interplay between mucus mobility and alveolar macrophage targeting of surface-modified liposomes. Journal of controlled release, 352, 15–24.
  • Jara, M.O., et al., 2021. Niclosamide inhalation powder made by thin-film freezing: Multi-dose tolerability and exposure in rats and pharmacokinetics in hamsters. International journal of pharmaceutics, 603, 120701.
  • Javadzadeh, Y., and Yaqoubi, S., 2017. Therapeutic nanostructures for pulmonary drug delivery. In: Ecaterina Andronescu and Alexandru Mihai Grumezescu, eds. Nanostructures for drug delivery. Elsevier Science, 619–638.
  • Ji, Y.L., et al., 2021. The pathogenesis and treatment of COVID-19: a system review. Biomedical and environmental sciences, 34 (1), 50.
  • Jones, M.N., et al., 1994. The targeting of phospholipid liposomes to bacteria. Biochimica et biophysica acta, 1196 (1), 57–64.
  • Kale, A.A., and Torchilin, V.P., 2007. Enhanced transfection of tumor cells in vivo using ‘Smart’ pH-sensitive TAT-modified pegylated liposomes. Journal of drug targeting, 15 (7–8), 538–545.
  • Kavanagh, O., et al., 2020. Inhaled hydroxychloroquine to improve efficacy and reduce harm in the treatment of COVID-19. Medical hypotheses, 143, 110110.
  • Klimke, A., et al., 2020. Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection. Medical hypotheses, 142, 109783.
  • Kulkarni, V., and Shaw, C., 2002. Guidance for industry nasal spray and inhalation solution, suspension, and spray drug products—chemistry, manufacturing, and controls documentation. https://www.fda.gov/files/drugs/published/Nasal-Spray-and-Inhalation-Solution--Suspension--and-Drug-Products.pdf
  • Kuzmov, A., and Minko, T., 2015. Nanotechnology approaches for inhalation treatment of lung diseases. Journal of controlled release, 219, 500–518.
  • Labana, S., et al., 2002. Chemotherapeutic activity against murine tuberculosis of once weekly administered drugs (isoniazid and rifampicin) encapsulated in liposomes. International journal of antimicrobial agents, 20 (4), 301–304.
  • Labiris, N.R., and Dolovich, M.B., 2003. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications. British Journal of clinical pharmacology, 56 (6), 588–599.
  • Laska, I.F., et al., 2019. The efficacy and safety of inhaled antibiotics for the treatment of bronchiectasis in adults: a systematic review and meta-analysis. The lancet respiratory medicine, 7 (10), 855–869.
  • Lee, M.K., 2020. Liposomes for enhanced bioavailability of water-insoluble drugs: in vivo evidence and recent approaches. Pharmaceutics, 12 (3), 264.
  • Lehofer, B., et al., 2014. Impact of atomization technique on the stability and transport efficiency of nebulized liposomes harboring different surface characteristics. European journal of pharmaceutics and biopharmaceutics, 88 (3), 1076–1085.
  • Lei, C., et al., 2020. Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig. Nature Communications, 11 (1), 2070.
  • Li, H., et al., 2020. Coronavirus disease 2019 (COVID-19): current status and future perspectives. International journal of antimicrobial agents, 55 (5), 105951.
  • Li, J., et al., 2021a. Liposomal remdesivir inhalation solution for targeted lung delivery as a novel therapeutic approach for COVID-19. Asian journal of pharmaceutical sciences, 16 (6), 772–783.
  • Li, J., Zheng, H., and Leung, S.S.Y., 2022. Pulmonary delivery of emerging antibacterials for bacterial lung infections treatment. Pharmaceutical research, https://doi.org/10.1007/s11095-022-03379-8
  • Li, Z., Perkins, W., and Cipolla, D., 2021b. Robustness of aerosol delivery of amikacin liposome inhalation suspension using the eFlow® Technology. European journal of pharmaceutics and biopharmaceutics, 166, 10–18.
  • Lin, H.L., et al., 2020. Hypertonic saline enhances the efficacy of aerosolized gentamicin against Pseudomonas aeruginosa. Scientific reports, 10 (1), 4325.
  • Lo, Y.L., Tsai, J.C., and Kuo, J.H., 2004. Liposomes and disaccharides as carriers in spray-dried powder formulations of superoxide dismutase. Journal of controlled release, 94 (2–3), 259–272.
  • Lotfi, M., Hamblin, M.R., and Rezaei, N., 2020. COVID-19: Transmission, prevention, and potential therapeutic opportunities. Clinica Chimica Acta, 508, 254–266.
  • Lourenço, R.V., and Cotromanes, E., 1982. Clinical aerosols: I. Characterization of aerosols and their diagnostic uses. Archives of internal medicine, 142 (12), 2163–2172.
  • Matsuyama, S., et al., 2020. The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting the viral replication-transcription complex in cultured cells. Journal of virology, 95 (1), e01648–20.
  • Meers, P., et al., 2008. Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. The journal of antimicrobial chemotherapy, 61 (4), 859–868.
  • Mehta, P.P., et al., 2020. Recent advances in inhalable liposomes for treatment of pulmonary diseases: concept to clinical stance. Journal of drug delivery science and technology, 56, 101509.
  • Meissa Vaccines Inc., 2021. Safety and immunogenicity of an intranasal RSV vaccine expressing SARS-CoV-2 spike protein (COVID-19 vaccine) in adults. https://clinicaltrials.gov/ct2/show/NCT04798001
  • Miles, L.A., et al., 2014. New insights into the role of Plg-RKT in macrophage recruitment. International review of cell and molecular biology, 309, 259–302.
  • Mizgerd, J.P., 2006. Lung infection—a public health priority. PLOS medicine, 3 (2), e76.
  • Morais Da Silva, D.M., et al., 2018. Development of ciprofloxacin-loaded poly(vinyl alcohol) dry powder formulations for lung delivery. International journal of pharmaceutics, 547 (1-2), 114–121.
  • Müllertz, O.A.O., et al., 2023. Pulmonary administration of the liposome-based adjuvant CAF01: effect of surface charge on mucosal adjuvant function. Molecular pharmaceutics, 20 (2), 953–970.
  • Murgia, X., et al., 2018. The role of mucus on drug transport and its potential to affect therapeutic outcomes. Advanced drug delivery reviews, 124, 82–97.
  • Nakhaei, P., et al., 2021. Liposomes: Structure, biomedical applications, and stability parameters with emphasis on cholesterol. Frontiers in bioengineering and biotechnology, 9, 748.
  • Nanjwade, B.K., et al., 2011. Pulmonary drug delivery: novel pharmaceutical technologies breathe new life into the lungs. PDA journal of pharmaceutical science and technology, 65 (5), 513–534.
  • NCT04338828. 2022. Nitric oxide inhalation therapy for COVID-19 infections in the ED. https://clinicaltrials.gov/ct2/show/NCT04338828.
  • NCT04355637. 2020. Inhaled corticosteroid treatment of COVID19 patients with pneumonia. https://clinicaltrials.gov/show/NCT04355637.
  • NCT04356833. 2022. Nebulised Rt-PA for ARDS Due to COVID-19. https://clinicaltrials.gov/ct2/show/NCT04356833.
  • NCT04445246. 2022. Inhaled iloprost for suspected COVID-19 respiratory failure. https://clinicaltrials.gov/ct2/show/NCT04445246.
  • NCT04469491. 2020. Treatment of COVID-19 by nebulization of inteferon beta 1b efficiency and safety study. https://clinicaltrials.gov/show/NCT04469491.
  • NCT04527471. 2020. Study of ensifentrine or placebo delivered via pMDI in hospitalized patients with COVID-19. https://clinicaltrials.gov/show/NCT04527471.
  • NCT04635241. 2022. Inhaled heparin for hospitalised COVID-19 patients. https://clinicaltrials.gov/ct2/show/NCT04635241.
  • NCT04679909. 2022. Safety and immunogenicity of AdCOVID in healthy adults (COVID-19 Vaccine Study). https://clinicaltrials.gov/ct2/show/NCT04679909.
  • NCT04681053. 2022. Inhaled Ivermectin and COVID-19. https://clinicaltrials.gov/ct2/show/NCT04681053.
  • NCT04707664. 2022. Sargramostim use in COVID-19 to recover patient health. https://clinicaltrials.gov/ct2/show/NCT04707664.
  • NCT04731051. 2021. The potential use of inhaled hydroxychloroquine for the treatment of COVID-19 in cancer patients. https://clinicaltrials.gov/show/NCT04731051.
  • NCT04751682. 2021. Safety and Immunogenicity of an Intranasal SARS-CoV-2 Vaccine (BBV154) for COVID-19. https://clinicaltrials.gov/ct2/show/NCT04751682
  • NCT04844580. 2022. A clinical study evaluating inhaled aviptadil on COVID-19. https://clinicaltrials.gov/ct2/show/NCT04844580
  • Newman, S.P., 2017. Drug delivery to the lungs: challenges and opportunities. Therapeutic delivery, 8 (8), 647–661.
  • NICE. 2022a. AZOTRENEM-BNF is only available in the UK. https://www.nice.org.uk/bnf-uk-only
  • NICE. 2022b. BNF is only available in the UK. https://www.nice.org.uk/bnf-uk-only
  • NICE. 2022c. Colistimethate sodium-BNF is only available in the UK. https://www.nice.org.uk/bnf-uk-only.
  • Nicolau, D.V., and Bafadhel, M., 2020. Inhaled corticosteroids in virus pandemics: a treatment for COVID-19? The lancet respiratory medicine, 8 (9), 846–847.
  • O’Callaghan, C., and Barry, P., 1997. The science of nebulised drug delivery. Thorax, 52 (Supplement 2), 31–31.
  • Orienti, I., Gentilomi, G.A., and Farruggia, G., 2020. Pulmonary delivery of fenretinide: a possible adjuvant treatment in COVID-19. International journal of molecular sciences, 21 (11), 3812.
  • Ourique, A.F., et al., 2014. Redispersible liposomal-N-acetylcysteine powder for pulmonary administration: development, in vitro characterization and antioxidant activity. European journal of pharmaceutical sciences, 65, 174–182.
  • Pandey, R., Sharma, S., and Khuller, G.K., 2004. Liposome-based antitubercular drug therapy in a guinea pig model of tuberculosis. International journal of antimicrobial agents, 23 (4), 414–415.
  • Parikh, R., et al., 2020. Inhaled nitric oxide treatment in spontaneously breathing COVID-19 patients. Therapeutic advances in respiratory disease, 14, 175346662093351.
  • Parvathaneni, V., et al., 2021. Therapeutic potential of inhalable medications to combat coronavirus disease-2019. Therapeutic delivery, 12 (2), 105–110.
  • Patel, A., et al., 2020. In vitro and in vivo antitubercular activity of benzothiazinone-loaded human serum albumin nanocarriers designed for inhalation. Journal of controlled release, 328, 339–349.
  • Patil, J.S., and Sarasija, S., 2012. Pulmonary drug delivery strategies: a concise, systematic review. Lung India, 29 (1), 44–49.
  • Patton, J.S., 1996. Mechanisms of macromolecule absorption by the lungs. Advanced drug delivery reviews, 19 (1), 3–36.
  • Patton, J.S., et al., 2010. The particle has landed–characterizing the fate of inhaled pharmaceuticals. Journal of aerosol medicine and pulmonary drug delivery, 23 (S2), S-71–S-87.
  • Peña-Silva, R., et al., 2021. Pharmacokinetic considerations on the repurposing of ivermectin for treatment of COVID-19. British journal of clinical pharmacology, 87 (3), 1589–1590.
  • Pérez, B.F., et al., 2014. Mucociliary clearance system in lung defense. Revista medica de chile, 142 (5), 606–615.
  • Pham, D.D., Fattal, E., and Tsapis, N., 2015. Pulmonary drug delivery systems for tuberculosis treatment. International journal of pharmaceutics, 478 (2), 517–529.
  • Pindiprolu, S.K.S.S., et al., 2020. Pulmonary delivery of nanostructured lipid carriers for effective repurposing of salinomycin as an antiviral agent. Medical hypotheses, 143, 109858.
  • Price, D.N., and Muttil, P., 2018. Delivery of therapeutics to the lung. Methods in molecular biology, 1809, 415–429.
  • Puri, A., et al., 2009. Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic. Critical reviews in therapeutic drug carrier systems, 26 (6), 523–580.
  • Que, H., et al., 2022. Tripterin liposome relieves severe acute respiratory syndrome as a potent COVID-19 treatment. Signal transduction and targeted therapy, 7 (1), 399.
  • Rabiei, M., et al., 2022. Characteristics of SARS-CoV2 that may be useful for nanoparticle pulmonary drug delivery. Journal of drug targeting, 30 (3), 233–243.
  • Ramakrishnan, S., et al., 2021. Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. The lancet respiratory medicine, 9 (7), 763–772.
  • Rangaraj, N., Pailla, S.R., and Sampathi, S., 2019. Insight into pulmonary drug delivery: mechanism of drug deposition to device characterization and regulatory requirements. Pulmonary pharmacology & therapeutics, 54, 1–21.
  • Rau, J.L., 2005. The inhalation of drugs: Advantages and problems. Respiratory care, 50 (3), 367–382.
  • Reshna, K.R., Balakrishnan, P., and Gopi, S., 2022. Systematic review on activity of liposomal encapsulated antioxidant, antibiotics, and antiviral agents. Journal of liposome research, 32 (4), 340–353.
  • Robinson, J., 2004. Colonization and infection of the respiratory tract: what do we know? Paediatrics & child health, 9 (1), 21–24.
  • Rossi, I., et al., 2019. Sodium hyaluronate nanocomposite respirable microparticles to tackle antibiotic resistance with potential application in treatment of mycobacterial pulmonary infections. Pharmaceutics, 11 (5), 203.
  • Rudokas, M., et al., 2016. Liposome delivery systems for inhalation: a critical review highlighting formulation issues and anticancer applications. Medical principles and practice, 25 (Suppl 2), 60–72.
  • Saari, M., et al., 1999. Pulmonary distribution and clearance of two beclomethasone liposome formulations in healthy volunteers. International journal of pharmaceutics, 181 (1), 1–9.
  • Sachetelli, S., et al., 2000. Demonstration of a fusion mechanism between a fluid bactericidal liposomal formulation and bacterial cells. Biochimica et biophysica acta, 1463 (2), 254–266.
  • Sacks, L.V., et al., 2001. Adjunctive salvage therapy with inhaled aminoglycosides for patients with persistent smear-positive pulmonary tuberculosis. Clinical infectious diseases, 32 (1), 44–49.
  • Sahakijpijarn, S., et al., 2020. Development of remdesivir as a dry powder for inhalation by thin film freezing. Pharmaceutics, 12 (11), 1002.
  • Sarcinelli, M.A., et al., 2021. The pulmonary route as a way to drug repositioning in COVID-19 therapy. Journal of drug delivery science and technology, 63, 102430.
  • Shaffer, C., 2020. Mist begins to clear for lung delivery of RNA. Nature biotechnology, 38 (10), 1110–1112.
  • Shah, S., et al., 2021. Development and optimization of inhalable levofloxacin nanoparticles for the treatment of tuberculosis. Current drug delivery, 18 (6), 779–793.
  • Sharma, A., et al., 2021. Advances in pulmonary drug delivery targeting microbial biofilms in respiratory diseases. Nanomedicine, 16 (21), 1905–1923.
  • Sheth, P., et al., 2017. Influence of formulation factors on the aerosol performance of suspension and solution metered dose inhalers: a systematic approach. The AAPS journal, 19 (5), 1396–1410.
  • Surendrakumar, K., et al., 2003. Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs. Journal of controlled release, 91 (3), 385–394.
  • Swathi Krishna, S., Thennavan, A., and Kanthlal, S.K., 2022. Dietary foods containing nitric oxide donors can be early curators of SARS-CoV-2 infection: a possible role in the immune system. Journal of food biochemistry, 46 (3), e13884.
  • Tai, T.T., et al., 2021. A Strategy to treat COVID-19 disease with targeted delivery of inhalable liposomal hydroxychloroquine: a preclinical pharmacokinetic study. Clinical and translational science, 14 (1), 132–136.
  • Tamura, G., 2015. Comparison of the aerosol velocity of Respimat® soft mist inhaler and seven pressurized metered dose inhalers. Allergology international, 64 (4), 390–392.
  • Tashkin, D.P., Koltun, A., and Wallace, R., 2021. A generic fluticasone propionate and salmeterol dry powder inhaler: evidence of usability, function, and robustness. Allergy and asthma proceedings, 42 (1), 30–35.
  • Tolman, J.A., and Williams, R.O., 2010. Advances in the pulmonary delivery of poorly water-soluble drugs: influence of solubilization on pharmacokinetic properties. Drug development and industrial pharmacy, 36 (1), 1–30.
  • U.S. Department of Health and Human Services. 1998. Metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products: chemistry, manufacturing, and controls documentation. https://www.hhs.gov/guidance/document/metered-dose-inhaler-mdi-and-dry-powder-inhaler-dpi-drug-products-quality-considerations
  • Ungaro, F., et al., 2012. Dry powders based on PLGA nanoparticles for pulmonary delivery of antibiotics: modulation of encapsulation efficiency, release rate and lung deposition pattern by hydrophilic polymers. Journal of controlled release, 157 (1), 149–159.
  • US FDA. 2016. Guidance on fluticasone propionate; salmeterol xinafoate. US Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/psg/PSG_208799.pdf
  • Van Haren, F.M.P., et al., 2020. Nebulised heparin as a treatment for COVID-19: scientific rationale and a call for randomised evidence. Critical Care, 24 (1), 454.
  • Vartak, R., et al., 2021. Aerosolized nanoliposomal carrier of remdesivir: an effective alternative for COVID-19 treatment in vitro. Nanomedicine, 16 (14), 1187–1202.
  • Velkov, T., et al., 2015. Inhaled anti-infective chemotherapy for respiratory tract infections: successes, challenges and the road ahead. Advanced drug delivery reviews, 85, 65–82.
  • .Vila, T.V.M. and Rozental, S., 2016. Biofilm formation as a pathogenicity factor of medically important fungi. In: S. Sultan, ed. Fungal Pathogenicity. London, England: InTech.
  • Viswanathan, V., et al., 2019. Inhalable liposomes of Glycyrrhiza glabra extract for use in tuberculosis: formulation, in vitro characterization, in vivo lung deposition, and in vivo pharmacodynamic studies. Drug development and industrial pharmacy, 45 (1), 11–20.
  • WebMD. 1987. Ipratropium bromide inhalation is ineffective. InPharma, 599 (1), 17–17.
  • Weers, J., and Tarara, T., 2014. The PulmoSphereTM platform for pulmonary drug delivery. Therapeutic delivery, 5 (3), 277–295.
  • WHO. 2022. Coronavirus disease – answers. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/coronavirus-disease-answers?
  • Wu, R., et al., 2020a. An update on current therapeutic drugs treating COVID-19. Current pharmacology reports, 6 (3), 56–70.
  • Wu, Y., et al., 2020b. Plasminogen improves lung lesions and hypoxemia in patients with COVID-19. QJM, 113 (8), 539–545.
  • Xie, J., et al., 2022. Cholesterol microdomain enhances the biofilm eradication of antibiotic liposomes. Advanced healthcare materials, 11 (8), e2101745.
  • Yıldız-Peköz, A., and Ehrhardt, C., 2020. Advances in pulmonary drug delivery. Pharmaceutics, 12 (10), 911.
  • Yu, L.M., et al., 2021. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet, 398 (10303), 843–855.
  • Yu, T., et al., 2015. Liposome-based mucus-penetrating particles (MPP) for mucosal theranostics: Demonstration of diamagnetic chemical exchange saturation transfer (diaCEST) magnetic resonance imaging (MRI). Nanomedicine, 11 (2), 401–405.
  • Yuen, C.K., et al., 2020. SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists. Emerging microbes & infections, 9 (1), 1418–1428.
  • Zhang, J., et al., 2018. Amikacin Liposome Inhalation Suspension (ALIS) penetrates non-tuberculous mycobacterial biofilms and enhances amikacin uptake into macrophages. Frontiers in microbiology, 9 (MAY), 915.
  • Zhang, W., et al., 2020. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerging microbes & infections, 9 (1), 386–389.
  • Zhao, J., et al., 2022. Elucidating inhaled liposome surface charge on its interaction with biological barriers in the lung. European journal of pharmaceutics and biopharmaceutics, 172, 101–111.
  • Zhou, P., et al., 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579 (7798), 270–273.
  • Zhou, Q.T., et al., 2015. Inhaled formulations and pulmonary drug delivery systems for respiratory infections. Advanced drug delivery reviews, 85, 83–99.
  • Zhu, F., 2021. Phase I/II clinical trial of recombinant novel coronavirus (COVID-19) vaccine (adenovirus type 5 vector) for inhalation. https://clinicaltrials.gov/show/NCT04840992.
  • Zhu, Y.-G., Shi, M.-M., Monsel, A., Dai, C.-X., Dong, X., Shen, H., Li, S.-K., Chang, J., Xu, C.-L., Li, P., Wang, J., Shen, M.-P., Ren, C.-J., Chen, D.-C., and Qu, J.-M., 2022. Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study. Stem cell research & therapy, 13 (1).

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