Skip to main content

Advertisement

SpringerLink
Log in

Nanotechnology Enabled Inhalation of Bio-therapeutics for Pulmonary Diseases: Design Considerations and Challenges

  • Nanoparticle-based Drug Delivery (R Banerjee, Section Editor)
  • Published:
Current Pathobiology Reports

Abstract

Purpose of Review

This review aims to critically discuss design considerations for the development of nanoparticle-based formulations for inhalation delivery of bio-therapeutics in pulmonary diseases. We will also discuss the challenges towards clinical translation of this approach, highlighting the directions for future research.

Recent Findings

Nanotechnology-based inhalation delivery of bio-therapeutics in pulmonary diseases can potentially overcome the shortcomings of clinically used parenteral route. Exploration of inhalable nanoparticles for delivery of bio-therapeutics in pulmonary diseases is still at an early stage. While most of these approaches have been developed for the delivery of nucleic acids, a few have focused on delivering monoclonal antibodies and proteins. However, multiple challenges need to be addressed for successful translation of this approach.

Summary

We summarize the design considerations and challenges that may help in creating a roadmap for the development of clinically translatable nanoparticle-based inhalable formulations of bio-therapeutics for pulmonary diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Zugazagoitia J, Molina-Pinelo S, Lopez-Rios F, Paz-Ares L. Biological therapies in nonsmall cell lung cancer. Eur Respir J. 2017. https://doi.org/10.1183/13993003.01520-2016.

  2. Quon BS, Rowe SM. New and emerging targeted therapies for cystic fibrosis. BMJ. 2016;352:i859. https://doi.org/10.1136/bmj.i859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Pavord ID. Biologics and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2018;141:1983–91. https://doi.org/10.1016/j.jaci.2018.04.020.

    Article  PubMed  Google Scholar 

  4. McCracken JL, Tripple JW, Calhoun WJ. Biologic therapy in the management of asthma. Curr Opin Allergy Clin Immunol. 2016;16:375–82. https://doi.org/10.1097/ACI.0000000000000284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fellner RC, Terryah ST, Tarran R. Inhaled protein/peptide-based therapies for respiratory disease. Mol Cell Pediatr. 2016;3:16. https://doi.org/10.1186/s40348-016-0044-8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Guilleminault L, Azzopardi N, Arnoult C, Sobilo J, Hervé V, Montharu J, et al. Fate of inhaled monoclonal antibodies after the deposition of aerosolized particles in the respiratory system. J Control Release. 2014;196:344–54. https://doi.org/10.1016/j.jconrel.2014.10.003.

    Article  CAS  PubMed  Google Scholar 

  7. •• Desoubeaux G, Reichert JM, Sleeman M, et al. Therapeutic monoclonal antibodies for respiratory diseases: current challenges and perspectives, March 31 - April 1, 2016, Tours, France. MAbs. 2016;8:999–1009. https://doi.org/10.1080/19420862.2016.1196521 This comprehensive report from a meeting emphasizes why inhalation delivery of monoclonal antibodies in pulmonary diseases deserves further investigation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Matucci A, Nencini F, Pratesi S, Maggi E, Vultaggio A. An overview on safety of monoclonal antibodies. Curr Opin Allergy Clin Immunol. 2016;16:576–81. https://doi.org/10.1097/ACI.0000000000000315.

    Article  CAS  PubMed  Google Scholar 

  9. Niebecker R, Kloft C. Safety of therapeutic monoclonal antibodies. Curr Drug Saf. 2010;5:275–86.

    Article  CAS  PubMed  Google Scholar 

  10. Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJT. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov. 2010;9:325–38. https://doi.org/10.1038/nrd3003.

    Article  CAS  Google Scholar 

  11. Gu T, Shah N, Deshpande G, Tang DH, Eisenberg DF. Comparing biologic cost per treated patient across indications among adult US managed care patients: a retrospective cohort study. Drugs - real world outcomes. 2016;3:369–81. https://doi.org/10.1007/s40801-016-0093-2.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet (London, England). 2007;370:1422–31. https://doi.org/10.1016/S0140-6736(07)61600-6.

    Article  CAS  Google Scholar 

  13. Lightwood D, Tservistas M, Zehentleitner M, Sarkar K, Turner A, Bracher M, et al. Efficacy of an inhaled IL-13 antibody fragment in a model of chronic asthma. Am J Respir Crit Care Med. 2018;198:610–9. https://doi.org/10.1164/rccm.201712-2382OC.

    Article  PubMed  Google Scholar 

  14. Leyva-Grado VH, Tan GS, Leon PE, Yondola M, Palese P. Direct administration in the respiratory tract improves efficacy of broadly neutralizing anti-influenza virus monoclonal antibodies. Antimicrob Agents Chemother. 2015;59:4162–72. https://doi.org/10.1128/AAC.00290-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fahy JV, Cockcroft DW, Boulet LP, Wong HH, Deschesnes F, Davis EE, et al. Effect of aerosolized anti-IgE (E25) on airway responses to inhaled allergen in asthmatic subjects. Am J Respir Crit Care Med. 1999;160:1023–7. https://doi.org/10.1164/ajrccm.160.3.9810012.

    Article  CAS  PubMed  Google Scholar 

  16. Respaud R, Marchand D, Parent C, Pelat T, Thullier P, Tournamille JF, et al. Effect of formulation on the stability and aerosol performance of a nebulized antibody. MAbs. 2014;6:1347–55. https://doi.org/10.4161/mabs.29938.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Rajapaksa AE, Ho JJ, Qi A, Bischof R, Nguyen TH, Tate M, et al. Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization. Respir Res. 2014;15:60. https://doi.org/10.1186/1465-9921-15-60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cortez-Jugo C, Qi A, Rajapaksa A, Friend JR, Yeo LY. Pulmonary monoclonal antibody delivery via a portable microfluidic nebulization platform. Biomicrofluidics. 2015;9:52603. https://doi.org/10.1063/1.4917181.

    Article  CAS  Google Scholar 

  19. Koussoroplis SJ, Paulissen G, Tyteca D, Goldansaz H, Todoroff J, Barilly C, et al. PEGylation of antibody fragments greatly increases their local residence time following delivery to the respiratory tract. J Control Release. 2014;187:91–100. https://doi.org/10.1016/j.jconrel.2014.05.021.

    Article  CAS  PubMed  Google Scholar 

  20. Duncan GA, Jung J, Hanes J, Suk JS. The mucus barrier to inhaled gene therapy. Mol Ther. 2016;24:2043–53. https://doi.org/10.1038/mt.2016.182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Schneider CS, Xu Q, Boylan NJ, Chisholm J, Tang BC, Schuster BS, et al. Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation. Sci Adv. 2017;3:e1601556. https://doi.org/10.1126/sciadv.1601556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Huang X, Chisholm J, Zhuang J, Xiao Y, Duncan G, Chen X, et al. Protein nanocages that penetrate airway mucus and tumor tissue. Proc Natl Acad Sci. 2017;114:E6595–602. https://doi.org/10.1073/pnas.1705407114.

    Article  CAS  PubMed  Google Scholar 

  23. Joshi N, Kaur S, Banerjee R. Advances in sub-micron particle based aerosol strategies for efficient systemic delivery of therapeutic agents. Curr Pharm Des. 2016;22:2470–80.

    Article  CAS  PubMed  Google Scholar 

  24. Joshi N. Can nanotechnology hit the spot in aerosol-based drug delivery for lung disorders? Ther Deliv. 2018;9:233–6. https://doi.org/10.4155/tde-2017-0112.

    Article  CAS  PubMed  Google Scholar 

  25. • Conti DS, Brewer D, Grashik J, Avasarala S, da Rocha SRP. Poly(amidoamine) dendrimer nanocarriers and their aerosol formulations for siRNA delivery to the lung epithelium. Mol Pharm. 2014;11:1808–22. https://doi.org/10.1021/mp4006358 This study demonstrates the the developemnet of a nanoparticle paltfordm for siRNA delivery to lung epithelium.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Xu C-X, Jere D, Jin H, Chang SH, Chung YS, Shin JY, et al. Poly(ester amine)-mediated, aerosol-delivered Akt1 small interfering RNA suppresses lung tumorigenesis. Am J Respir Crit Care Med. 2008;178:60–73. https://doi.org/10.1164/rccm.200707-1022OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fernández Fernández E, Santos-Carballal B, de Santi C, Ramsey JM, MacLoughlin R, Cryan S-A, Greene CM. Biopolymer-based nanoparticles for cystic fibrosis lung gene therapy studies. Mater (Basel, Switzerland) 2018:11. Doi: https://doi.org/10.3390/ma11010122.

  28. Mottais A, Le Gall T, Sibiril Y, Ravel J, Laurent V, D’Arbonneau F, Montier T. Enhancement of lung gene delivery after aerosol: a new strategy using non-viral complexes with antibacterial properties. Biosci Rep 2017:37. Doi: https://doi.org/10.1042/BSR20160618.

  29. • Halwani R, Sultana Shaik A, Ratemi E, Afzal S, Kenana R, Al-Muhsen S, et al. A novel anti-IL4Rα nanoparticle efficiently controls lung inflammation during asthma. Exp Mol Med. 2016;48:e262. https://doi.org/10.1038/emm.2016.89 This study demonstrates the development of a nanoparticle platform for delivery of a monoclonal antibody in asthma.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kuzmov A, Minko T. Nanotechnology approaches for inhalation treatment of lung diseases. J Control Release. 2015;219:500–18. https://doi.org/10.1016/j.jconrel.2015.07.024.

    Article  CAS  PubMed  Google Scholar 

  31. Omlor AJ, Nguyen J, Bals R, Dinh QT. Nanotechnology in respiratory medicine. Respir Res. 2015;16:64. https://doi.org/10.1186/s12931-015-0223-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Richards DA, Maruani A, Chudasama V. Antibody fragments as nanoparticle targeting ligands: a step in the right direction. Chem Sci. 2017;8:63–77. https://doi.org/10.1039/c6sc02403c.

    Article  CAS  PubMed  Google Scholar 

  33. Schwendener RA, Schott H. Liposome formulations of hydrophobic drugs. Methods Mol Biol. 2010;605:129–38. https://doi.org/10.1007/978-1-60327-360-2_8.

    Article  CAS  PubMed  Google Scholar 

  34. Sahana DK, Mittal G, Bhardwaj V, Kumar MNVR. PLGA nanoparticles for oral delivery of hydrophobic drugs: influence of organic solvent on nanoparticle formation and release behavior in vitro and in vivo using estradiol as a model drug. J Pharm Sci. 2008;97:1530–42. https://doi.org/10.1002/jps.21158.

    Article  CAS  PubMed  Google Scholar 

  35. Sousa F, Castro P, Fonte P, Kennedy PJ, Neves-Petersen MT, Sarmento B. Nanoparticles for the delivery of therapeutic antibodies: dogma or promising strategy? Expert Opin Drug Deliv. 2017;14:1163–76. https://doi.org/10.1080/17425247.2017.1273345.

    Article  CAS  PubMed  Google Scholar 

  36. Haggag YA, Faheem AM. Evaluation of nano spray drying as a method for drying and formulation of therapeutic peptides and proteins. Front Pharmacol. 2015;6:140. https://doi.org/10.3389/fphar.2015.00140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Di Stasio E, De Cristofaro R. The effect of shear stress on protein conformation: physical forces operating on biochemical systems: the case of von Willebrand factor. Biophys Chem. 2010;153:1–8. https://doi.org/10.1016/j.bpc.2010.07.002.

    Article  CAS  PubMed  Google Scholar 

  38. Hertel SP, Winter G, Friess W. Protein stability in pulmonary drug delivery via nebulization. Adv Drug Deliv Rev. 2015;93:79–94. https://doi.org/10.1016/j.addr.2014.10.003.

    Article  CAS  PubMed  Google Scholar 

  39. Respaud R, Vecellio L, Diot P, Heuzé-Vourc’h N. Nebulization as a delivery method for mAbs in respiratory diseases. Expert Opin Drug Deliv. 2015;12:1027–39. https://doi.org/10.1517/17425247.2015.999039.

    Article  CAS  PubMed  Google Scholar 

  40. Poptsova MS, Il’icheva IA, Nechipurenko DY, Panchenko LA, Khodikov MV, Oparina NY, et al. Non-random DNA fragmentation in next-generation sequencing. Sci Rep. 2014;4:4532. https://doi.org/10.1038/srep04532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Patlolla RR, Chougule M, Patel AR, Jackson T, Tata PNV, Singh M. Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers. J Control Release. 2010;144:233–41. https://doi.org/10.1016/j.jconrel.2010.02.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ibrahim M, Verma R, Garcia-Contreras L. Inhalation drug delivery devices: technology update. Med Devices (Auckl). 2015;8:131–9. https://doi.org/10.2147/MDER.S48888.

    Article  CAS  Google Scholar 

  43. Dailey LA, Schmehl T, Gessler T, Wittmar M, Grimminger F, Seeger W, et al. Nebulization of biodegradable nanoparticles: impact of nebulizer technology and nanoparticle characteristics on aerosol features. J Control Release. 2003;86:131–44.

    Article  CAS  PubMed  Google Scholar 

  44. Courrier HM, Butz N, Vandamme TF. Pulmonary drug delivery systems: recent developments and prospects. Crit Rev Ther Drug Carrier Syst. 2002;19:425–98.

    Article  CAS  PubMed  Google Scholar 

  45. Tsapis N, Bennett D, Jackson B, Weitz DA, Edwards DA. Trojan particles: large porous carriers of nanoparticles for drug delivery. Proc Natl Acad Sci U S A. 2002;99:12001–5. https://doi.org/10.1073/pnas.182233999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wang Y, Kho K, Cheow WS, Hadinoto K. A comparison between spray drying and spray freeze drying for dry powder inhaler formulation of drug-loaded lipid-polymer hybrid nanoparticles. Int J Pharm. 2012;424:98–106. https://doi.org/10.1016/j.ijpharm.2011.12.045.

    Article  CAS  PubMed  Google Scholar 

  47. Chadha TS, Chattopadhyay S, Venkataraman C, Biswas P. Study of the charge distribution on liposome particles aerosolized by air-jet atomization. J Aerosol Med Pulm Drug Deliv. 2012;25:355–64. https://doi.org/10.1089/jamp.2011.0967.

    Article  CAS  PubMed  Google Scholar 

  48. Chattopadhyay S. Aerosol generation using nanometer liposome suspensions for pulmonary drug delivery applications. J Liposome Res. 2013;23:255–67. https://doi.org/10.3109/08982104.2013.802332.

    Article  CAS  PubMed  Google Scholar 

  49. Iyer R, Hsia CCW, Nguyen KT. Nano-therapeutics for the lung: state-of-the-art and future perspectives. Curr Pharm Des. 2015;21:5233–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Yamamoto H, Kuno Y, Sugimoto S, Takeuchi H, Kawashima Y. Surface-modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin by mucoadhesion and opening of the intercellular tight junctions. J Control Release. 2005;102:373–81. https://doi.org/10.1016/j.jconrel.2004.10.010.

    Article  CAS  PubMed  Google Scholar 

  51. Joshi N, Shanmugam T, Kaviratna A, Banerjee R. Proapoptotic lipid nanovesicles: synergism with paclitaxel in human lung adenocarcinoma A549 cells. J Control Release. 2011;156:413–20. https://doi.org/10.1016/j.jconrel.2011.07.025.

    Article  CAS  PubMed  Google Scholar 

  52. Joshi N, Shirsath N, Singh A, Joshi KS, Banerjee R. Endogenous lung surfactant inspired pH responsive nanovesicle aerosols: pulmonary compatible and site-specific drug delivery in lung metastases. Sci Rep. 2014;4:7085. https://doi.org/10.1038/srep07085.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Sethi M, Sukumar R, Karve S, Werner ME, Wang EC, Moore DT, et al. Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity. Nanoscale. 2014;6:2321–7. https://doi.org/10.1039/c3nr05961h.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Serruys PW, Sianos G, Abizaid A, Aoki J, den Heijer P, Bonnier H, et al. The effect of variable dose and release kinetics on neointimal hyperplasia using a novel paclitaxel-eluting stent platform: the paclitaxel in-stent controlled elution study (PISCES). J Am Coll Cardiol. 2005;46:253–60. https://doi.org/10.1016/j.jacc.2005.03.069.

    Article  CAS  PubMed  Google Scholar 

  55. Varshochian R, Jeddi-Tehrani M, Mahmoudi AR, Khoshayand MR, Atyabi F, Sabzevari A, et al. The protective effect of albumin on bevacizumab activity and stability in PLGA nanoparticles intended for retinal and choroidal neovascularization treatments. Eur J Pharm Sci. 2013;50:341–52. https://doi.org/10.1016/j.ejps.2013.07.014.

    Article  CAS  PubMed  Google Scholar 

  56. Lai SK, Wang Y-Y, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev. 2009;61:158–71. https://doi.org/10.1016/j.addr.2008.11.002.

    Article  CAS  PubMed  Google Scholar 

  57. Porsio B, Craparo EF, Mauro N, Giammona G, Cavallaro G. Mucus and cell-penetrating nanoparticles embedded in nano-into-micro formulations for pulmonary delivery of Ivacaftor in patients with cystic fibrosis. ACS Appl Mater Interfaces. 2018;10:165–81. https://doi.org/10.1021/acsami.7b14992.

    Article  CAS  PubMed  Google Scholar 

  58. Kleemann E, Neu M, Jekel N, Fink L, Schmehl T, Gessler T, et al. Nano-carriers for DNA delivery to the lung based upon a TAT-derived peptide covalently coupled to PEG-PEI. J Control Release. 2005;109:299–316. https://doi.org/10.1016/j.jconrel.2005.09.036.

    Article  CAS  PubMed  Google Scholar 

  59. Selby LI, Cortez-Jugo CM, Such GK, Johnston APR. Nanoescapology: progress toward understanding the endosomal escape of polymeric nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2017;9. https://doi.org/10.1002/wnan.1452.

  60. Ma D. Enhancing endosomal escape for nanoparticle mediated siRNA delivery. Nanoscale. 2014;6:6415–25. https://doi.org/10.1039/c4nr00018h.

    Article  CAS  PubMed  Google Scholar 

  61. Chu Z, Miu K, Lung P, Zhang S, Zhao S, Chang H-C, et al. Rapid endosomal escape of prickly nanodiamonds: implications for gene delivery. Sci Rep. 2015;5:11661. https://doi.org/10.1038/srep11661.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Sahay G, Querbes W, Alabi C, Eltoukhy A, Sarkar S, Zurenko C, et al. Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat Biotechnol. 2013;31:653–8. https://doi.org/10.1038/nbt.2614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Card JW, Zeldin DC, Bonner JC, Nestmann ER. Pulmonary applications and toxicity of engineered nanoparticles. Am J Physiol Lung Cell Mol Physiol. 2008;295:L400–11. https://doi.org/10.1152/ajplung.00041.2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Li JJ, Muralikrishnan S, Ng C-T, Yung L-YL, Bay B-H. Nanoparticle-induced pulmonary toxicity. Exp Biol Med (Maywood). 2010;235:1025–33. https://doi.org/10.1258/ebm.2010.010021.

    Article  CAS  Google Scholar 

  65. Li JG, Li QN, Xu JY, Cai XQ, Liu RL, Li YJ, et al. The pulmonary toxicity of multi-wall carbon nanotubes in mice 30 and 60 days after inhalation exposure. J Nanosci Nanotechnol. 2009;9:1384–7.

    Article  CAS  PubMed  Google Scholar 

  66. Dailey LA, Jekel N, Fink L, Gessler T, Schmehl T, Wittmar M, et al. Investigation of the proinflammatory potential of biodegradable nanoparticle drug delivery systems in the lung. Toxicol Appl Pharmacol. 2006;215:100–8. https://doi.org/10.1016/j.taap.2006.01.016.

    Article  CAS  PubMed  Google Scholar 

  67. Dokka S, Toledo D, Shi X, Castranova V, Rojanasakul Y. Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes. Pharm Res. 2000;17:521–5.

    Article  CAS  PubMed  Google Scholar 

  68. Donaldson K, Murphy F, Schinwald A, Duffin R, Poland CA. Identifying the pulmonary hazard of high aspect ratio nanoparticles to enable their safety-by-design. Nanomedicine (Lond). 2011;6:143–56. https://doi.org/10.2217/nnm.10.139.

    Article  CAS  Google Scholar 

  69. Shah AR, Hagawane T, Kshirsagar N, Banerjee R. Surface-active drug loaded lipopolymeric nanohybrid aerosol therapy: potential non-invasive way to mitigate lipopolysaccharide mediated inflammation in murine lungs. RSC Adv. 2015;5:9683–94. https://doi.org/10.1039/C4RA13558J.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    N. Joshi

  2. Harvard Medical School, Boston, MA, 02115, USA

    N. Joshi

Authors
  1. N. Joshi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. Joshi.

Ethics declarations

Conflict of Interest

The author declares that there is no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

Additional information

This article is part of the Topical Collection on Nanoparticle-based Drug Delivery

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Joshi, N. Nanotechnology Enabled Inhalation of Bio-therapeutics for Pulmonary Diseases: Design Considerations and Challenges. Curr Pathobiol Rep 6, 225–231 (2018). https://doi.org/10.1007/s40139-018-0183-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40139-018-0183-9

Keywords

Search

Navigation