Pulmonary Drug Delivery: Formulations, Devices, Targeting Strategies, and Patient Compliance
DOI:
https://doi.org/10.22270/ajprd.v13i4.1596Abstract
Pulmonary drug delivery systems (PDDS) leverage the lungs' large surface area and rich vascularity for treating respiratory illnesses and systemic conditions. Benefits include rapid action, avoidance of first-pass metabolism, and fewer systemic side effects. PDDS are used for acute and chronic care, with new multi-drug devices improving adherence. Targeted delivery for macromolecules is evolving to boost local retention and reduce systemic exposure. Bypassing first-pass metabolism via the lungs significantly increases bioavailability, especially for vulnerable drugs like peptides. Sustained-release formulations are being developed to extend effects and improve adherence. Smart inhalers enhance monitoring and compliance. PDDS are also being explored for non-pulmonary systemic diseases, gene and RNA therapies for lung conditions, and aerosolized vaccines. Non-invasive inhalers improve patient compliance.Challenges in PDDS include airway structure affecting particle deposition, formulation issues with particle size and stability, patient technique and compliance, and drug properties impacting solubility and retention.New strategies like nanoparticles, liposomes, and other formulations enhance drug delivery. Device advancements (pMDIs, DPIs, nebulizers, smart inhalers) improve deposition and ease of use. Emerging methods like gene therapy and magnetic targeting offer precise delivery.
Downloads
References
Naghavi M, Antony C, Brauer M, Cohen A, Hay S, Krohn K, et al. Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019. eClinical Medicine. 2023 Apr 25;63:101936. doi: 10.1016/j.eclinm.2023.101936.
Dhege CT, Kumar P, Choonara YE. Pulmonary drug delivery devices and nanosystems as potential treatment strategies for acute respiratory distress syndrome (ARDS). Int J Pharm. 2024;657:124182. doi: 10.1016/j.ijpharm.2024.124182.
Rathod HK, Katekar VA, Dhole YR, Nalinde PS. Pulmonary drug delivery system: A review. GSC Biol Pharm Sci. 2023;25(3):149–58. doi: 10.30574/gscbps.2023.25.3.0473.
Sen O, Sarkar P, Das S, Giri NK, Sarkar S, Jana S, et al. Membrane permeability and drug targeting potential of phospholipid‐based nanocarriers in lung cancer therapy. ChemistrySelect. 2024;9(40). doi: 10.1002/slct.202403174.
Calle Rubio M, AdamiTeppa PJ, Rodríguez Hermosa JL, GarcíaCarro M, TallónMartínez JC, Riesco Rubio C, et al. Insights from real-world evidence on the use of inhalers in clinical practice. J Clin Med. 2025;14(4):1217. doi: 10.3390/jcm14041217.
Pham TQ, Delorme L, Cortaredona S, Ranque S, Menu E. Pulmonary aspergillosis: epidemiology and unresolved diagnostic challenges—insights from a two-year retrospective cohort study in Marseille. Respir Med. 2025;108206. doi: 10.1016/j.rmed.2025.108206.
Newman S. Drug delivery to the lungs: Challenges and opportunities. TherDeliv. 2017;8:647–61. doi: 10.4155/tde-2017-0037.
Jurado‐Palomo J, et al. A newly developed, easy‐to‐use prehospital drug‐derived score compared with three conventional scores: A prospective multicenter study. Eur J Clin Invest. 2025;55(1):e14329.
Banat H, Ambrus R, Csóka I. Drug combinations for inhalation: Current products and future development addressing disease control and patient compliance. Int J Pharm. 2023;643:123070. doi: 10.1016/j.ijpharm.2023.123070.
He S, Gui J, Xiong K, et al. A roadmap to pulmonary delivery strategies for the treatment of infectious lung diseases. J Nanobiotechnol. 2022;20:101. doi: 10.1186/s12951-022-01307-x.
Levin P, Hoogwerf BJ, Snell-Bergeon J, Vigers T, Pyle L, Bromberger L. Ultra rapid-acting inhaled insulin improves glucose control in patients with type 2 diabetes mellitus. EndocrPract. 2021;27(5):449–54. doi: 10.1016/j.eprac.2020.10.004.
Greene SF, Nikula KJ, Poulin D, McInally K, Reynolds JA. Long-term nonclinical pulmonary safety assessment of Afrezza, a novel insulin inhalation powder. ToxicolPathol. 2020;49(2):334–48. doi: 10.1177/0192623320960420.
Parthvi R, Mehra S. Technosphere insulin–induced pulmonary infiltrate. Am J Ther. 2021;28(6):e724–6. doi: 10.1097/MJT.0000000000001154.
Choudhury H, Pandey M, Chauhan N, Gorain B, Taneja S, Kesharwani P. Recent advances in microsphere-based inhalation therapy for treatment of pulmonary diseases. Drug Discov Today. 2023;28(9):103686. doi: 10.1016/j.drudis.2023.103686.
Weers J. Comparison of phospholipid-based particles for sustained release of ciprofloxacin following pulmonary administration to bronchiectasis patients. PulmTher. 2019;5:127–50. doi: 10.1007/s41030-019-00104-6.
Kumar Subramani P, P N R, Narayanasamy D. The role of pulmonary drug delivery in modern therapeutics: An overview. Cureus. 2024;16(9):e68639. doi: 10.7759/cureus.68639.
O’Connor L, Behar S, Tarrant S, et al. Rationale and design of Healthy at Home for COPD: An integrated remote patient monitoring and virtual pulmonary rehabilitation pilot study. Pilot Feasibility Stud. 2024;10:131. doi: 10.1186/s40814-024-01560-x.
Zhuang M, Hassan I, Ahmad WA, Abdul Kadir A, Liu X, Li F, et al. Effectiveness of digital health interventions for chronic obstructive pulmonary disease: Systematic review and meta-analysis. J Med Internet Res. 2025;27:e76323. doi: 10.2196/76323.
Gelbman BD, Reed CR. An integrated, multimodal, digital health solution for chronic obstructive pulmonary disease: Prospective observational pilot study. JMIR Form Res. 2022;6(3):e34758. doi: 10.2196/34758.
Sibiya N, Mbatha B, Ngubane P, Khathi A. Celebrating a century of insulin discovery: A critical appraisal of the emerging alternative insulin delivery systems. Curr Drug Deliv. 2023;20(6):656–68. doi: 10.2174/1567201819666220531101203.
Cooper W, Ray S, Aurora SK, Shrewsbury SB, Fuller C, Davies G, et al. Delivery of dihydroergotaminemesylate to the upper nasal space for the acute treatment of migraine: Technology in action. J Aerosol Med Pulm Drug Deliv. 2022;35(6):321–32. doi: 10.1089/jamp.2022.0005.
Agnihotri V, Agrawal Y, Goyal S, Sharma C, Ojha S. An update on advancements and challenges in inhalational drug delivery for pulmonary arterial hypertension. Molecules. 2022;27(11):3490. doi: 10.3390/molecules27113490.
Yang L, Zhang L, Luo Z. Comparative pharmacokinetics and bioequivalence evaluation of two formulations of pramipexoledi hydro chloride extended-release tablets in healthy Chinese subjects under fasted and fed states: A randomized, open-label, single-dose, two-period crossover clinical trial. Drug Des DevelTher. 2023;17:2369–81. doi: 10.2147/DDDT.S421449.
Liu F, Xin M, Feng H, Zhang W, Liao Z, Sheng T, et al. Cryo-shocked tumor cells deliver CRISPR-Cas9 for lung cancer regression by synthetic lethality. Sci Adv. 2024;10(13):eadk8264.doi: 10.1126/sciadv.adk8264. Epub 2024 Mar 29. PMID: 38552011; PMCID: PMC10980270.
Zhang YB, Xu D, Bai L, Zhou YM, Zhang H, Cui YL. A review of non-invasive drug delivery through respiratory routes. Pharmaceutics. 2022;14(9):1974. doi: 10.3390/pharmaceutics14091974.
Wei T, Sun Y, Cheng Q, Chatterjee S, Traylor Z, Johnson LT, et al. Lung SORT LNPs enable precise homology-directed repair mediated CRISPR/Cas genome correction in cystic fibrosis models. Nat Commun. 2023;14(1):7322. doi: 10.1038/s41467-023-42948-2.
Huayamares SG, Zenhausern R, Loughrey D. Nanocarriers for inhaled delivery of RNA therapeutics. Curr Res Biotechnol. 2024;7:100200. doi: 10.1016/j.crbiot.2024.100200.
Wang Y, Fu M, Liu J, Yang Y, Yu Y, Li J, et al. Inhibition of tumor metastasis by targeted daunorubicin and dioscincodelivery liposomes modified with PFV for the treatment of non-small-cell lung cancer. Int J Nanomedicine. 2019;14:4071–90. doi: 10.2147/IJN.S194304.
Hussen BM, Najmadden ZB, Abdullah SR, et al. CRISPR/Cas9 gene editing: a novel strategy for fighting drug resistance in respiratory disorders. Cell Commun Signal. 2024;22:329. doi: 10.1186/s12964-024-01713-8.
Huang C, Li H, Duan X, Zhang P, Qi S, Du J, et al. Inhaled non-viral delivery systems for RNA therapeutics. Acta Pharm Sin B. 2025;15(5):2402–30. doi: 10.1016/j.apsb.2025.03.033.
Heida R, Frijlink HW, Hinrichs WLJ. Inhalation of vaccines and antiviral drugs to fight respiratory virus infections: reasons to prioritize the pulmonary route of administration. mBio. 2023;14:e01295-23. doi: 10.1128/mbio.01295-23.
Klein TO, Soll BA, Issel BF, Fraser C. Bronchus-associated lymphoid tissue lymphoma and Mycobacterium tuberculosis infection: An unusual case and a review of the literature. Respir Care. 2007;52(6):755–8.
Counoupas C, Ferrell KC, Ashhurst A, et al. Mucosal delivery of a multistage subunit vaccine promotes development of lung-resident memory T cells and affords interleukin-17-dependent protection against pulmonary tuberculosis. NPJ Vaccines. 2020;5:105. doi: 10.1038/s41541-020-00255-7.
Zhou M, Xiao H, Yang X, Cheng T, Yuan L, Xia N. Novel vaccine strategies to induce respiratory mucosal immunity: advances and implications. MedComm (2020). 2025;6(2):e70056. doi: 10.1002/mco2.70056.
Overton ET, Goepfert PA, Cunningham P, Carter WA, Horvath J, Young D, et al. Intranasal seasonal influenza vaccine and a TLR-3 agonist, rintatolimod, induced cross-reactive IgA antibody formation against avian H5N1 and H7N9 influenza HA in humans. Vaccine. 2014;32(42):5490–5. doi: 10.1016/j.vaccine.2014.07.078.
Tero-Losada M, Petrovsky N, Alami A, Crispo JA, Mattison D, Capani F, et al. Disproportionality analysis of adverse neurological and psychiatric reactions with the ChAdOx1 (Oxford-AstraZeneca) and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines in the United Kingdom. Expert Opin Drug Saf. 2022;22(4):343–9. doi: 10.1080/14740338.2022.2120607.
Chen J, Wang P, Yuan L, Zhang L, Zhang L, Zhao H, et al. A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2. Sci Bull. 2022;67(13):1372–87. doi: 10.1016/j.scib.2022.05.018.
Setiabudiawan TP, Reurink RK, Hill PC, Netea MG, van Crevel R, Koeken VACM. Protection against tuberculosis by Bacillus CalmetteGuérin (BCG) vaccination: a historical perspective. Med (Cell Press). 2022;3(1):6–24. doi: 10.1016/j.medj.2021.11.006.
Yan R, Zou C, Yang X, Zhuang W, Huang Y, Zheng X, et al. Nebulized inhalation drug delivery: clinical applications and advancements in research. J Mater Chem B. 2025;13(3):821–43. doi: 10.1039/D4TB01938E.
Hagmeyer L, van Koningsbruggen-Rietschel S, Matthes S, Rietschel E, Randerath W. From the infant to the geriatric patient—strategies for inhalation therapy in asthma and chronic obstructive pulmonary disease. ClinRespir J. 2023;17(6):487–98. doi: 10.1111/crj.13610.
Burgess SW, Sly PD, Cooper DM, Devadason SG. Novel spacer device does not improve adherence in childhood asthma. PediatrPulmonol. 2007;42(8):736–9. doi: 10.1002/ppul.20647.
Schreiber J, Sonnenburg T, Luecke E. Inhaler devices in asthma and COPD patients – a prospective cross-sectional study on inhaler preferences and error rates. BMC Pulm Med. 2020;20:222. doi: 10.1186/s12890-020-01246-z.
Hodder R, Price D. Patient preferences for inhaler devices in chronic obstructive pulmonary disease: experience with Respimat Soft Mist inhaler. Int J Chron Obstruct Pulmon Dis. 2009;4:381–90. doi: 10.2147/copd.s3391.
Al-Tabakha MM. Future prospect of insulin inhalation for diabetic patients: The case of Afrezza versus Exubera. J Control Release. 2015;215:25–38. doi: 10.1016/j.jconrel.2015.07.025.
Chawhan A, Thakrar D, Pinto L. Inhaler devices and their challenges - Helping patients use inhalers. Lung India. 2023;40:303–5. doi: 10.4103/lungindia.lungindia_24_23.
Sosnowski TR. Towards more precise targeting of inhaled aerosols to different areas of the respiratory system. Pharmaceutics. 2024;16(1):97. doi: 10.3390/pharmaceutics16010097.
Farkas A, Balásházy I. Quantification of particle deposition in asymmetrical tracheobronchial model geometry. ComputBiol Med. 2008;38(4):508–18. doi: 10.1016/j.compbiomed.2008.01.014.
Zhou G, Liu Z, Shao W, Sun B, Li L, Liu J, et al. Study on the effects of dust particle size and respiratory intensity on the pattern of respiratory particle deposition in humans. Indoor Air. 2024. doi: 10.1155/2024/5025616.
Shen AM, Minko T. Pharmacokinetics of inhaled nanotherapeutics for pulmonary delivery. J Control Release. 2020;326:222–44. doi: 10.1016/j.jconrel.2020.07.011.
Boboltz A, Kumar S, Duncan GA. Inhaled drug delivery for the targeted treatment of asthma. Adv Drug Deliv Rev. 2023;198:114858. doi: 10.1016/j.addr.2023.114858.
Chang RYK, Chan HK. Advancements in particle engineering for inhalation delivery of small molecules and biotherapeutics. Pharm Res. 2022;39(12):3047–61. doi: 10.1007/s11095-022-03363-2.
Chang RYK, Chan HK. Advancements in particle engineering for inhalation delivery of small molecules and biotherapeutics. Pharm Res. 2022;39(12):3047–61. doi: 10.1007/s11095-022-03363-2.
Thevarkattil AM, Yousaf S, Houacine C, Khan W, Bnyan R, Elhissi A, et al. Anticancer drug delivery: Investigating the impacts of viscosity on lipid-based formulations for pulmonary targeting. Int J Pharm. 2024;664:124591. doi: 10.1016/j.ijpharm.2024.124591.
Çakmaklı S, Özdemir A, Fırat H, Aypak C. An evaluation of the use of inhalers in asthma and chronic obstructive pulmonary disease. J TaibahUniv Med Sci. 2023;18(4):860–7.
Published
How to Cite
Issue
Section
Copyright (c) 2025 Shubham Kamble, Archi Chaudhari, Diksha Mankar, Khushi Bagde

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
AUTHORS WHO PUBLISH WITH THIS JOURNAL AGREE TO THE FOLLOWING TERMS:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).