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Volume 2015, Issue 1
  • ISSN: 2305-7823
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Abstract

The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems.

© 2015 El-Sherbiny, El-Baz, Yacoub, licensee Bloomsbury Qatar Foundation Journals.
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2015-03-01
2024-04-20
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References

  1. Weers JG, Bell J, Chan H-K, Cipolla D, Dunbar C, Hickey AJ, Smith IJ. Pulmonary formulations: What remains to be done? Journal of Aerosol Medicine and Pulmonary Drug Delivery. 2010; 23:S2:S-5–S-23.
     [Google Scholar]
  2. Courrier H, Butz N, Vandamme TF. Pulmonary drug delivery systems: Recent developments and prospects. Critical Reviews in Therapeutic Drug Carrier Systems. 2002; 19:4-5.
     [Google Scholar]
  3. Ungaro F, d'Angelo I, Miro A, La Rotonda MI, Quaglia F. Engineered PLGA nano-and micro-carriers for pulmonary delivery: Challenges and promises. Journal of Pharmacy and Pharmacology. 2012; 64:9:1217–1235.
     [Google Scholar]
  4. Marieb EN, Hoehn K. Human anatomy & physiology. Pearson Education 2007.
     [Google Scholar]
  5. Smola M, Vandamme T, Sokolowski A. Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases. International Journal of Nanomedicine. 2008; 3:1:1.
     [Google Scholar]
  6. Paranjpe M, Müller-Goymann CC. Nanoparticle-mediated pulmonary drug delivery: A review. International Journal of Molecular Sciences. 2014; 15:4:5852–5873.
     [Google Scholar]
  7. McCorry LK. Essentials of human physiology for pharmacy. CRC Press 2004.
     [Google Scholar]
  8. The Respiratory System-How the lung works. 2012 [2 July]:1-7; Available from: http://www.nhlbi.nih.gov/health/health-topics/topics/hlw/system.html .
  9. El-Sherbiny IM, Villanueva DG, Herrera D, Smyth HD. Overcoming lung clearance mechanisms for controlled release drug delivery. Controlled pulmonary drug delivery. Springer 2011;:101–126.
     [Google Scholar]
  10. Patton JS, Brain JD, Davies LA, Fiegel J, Gumbleton M, Kim K-J, Sakagami M, Vanbever R, Ehrhardt C. The particle has landed—characterizing the fate of inhaled pharmaceuticals. Journal of Aerosol Medicine and Pulmonary Drug Delivery. 2010; 23:S2:S-71–S-87.
     [Google Scholar]
  11. Hogg J. Response of the lung to inhaled particles. The Medical Journal of Australia. 1985; 142:13:675–678.
     [Google Scholar]
  12. Olsson B, Bondesson E, Borgström L, Edsbäcker S, Eirefelt S, Ekelund K, Ekelund K, Gustavsson L, Hegelund-Myrbäck T. Pulmonary drug metabolism, clearance, and absorption. Controlled pulmonary drug delivery. Springer 2011;:21–50.
     [Google Scholar]
  13. Oberdörster G. Lung clearance of inhaled insoluble and soluble particles. Journal of Aerosol Medicine. 1988; 1:4:289–330.
     [Google Scholar]
  14. Parkinson A. Biotransformation of xenobiotics. New York: McGraw-Hill 2001.
     [Google Scholar]
  15. Wiedmann T, Bhatia R, Wattenberg L. Drug solubilization in lung surfactant. Journal of Controlled Release. 2000; 65:1:43–47.
     [Google Scholar]
  16. Patton JS. Mechanisms of macromolecule absorption by the lungs. Advanced Drug Delivery Reviews. 1996; 19:1:3–36.
     [Google Scholar]
  17. Patton JS, Byron PR. Inhaling medicines: Delivering drugs to the body through the lungs. Nature Reviews Drug Discovery. 2007; 6:1:67–74.
     [Google Scholar]
  18. Liao X, Wiedmann TS. Solubilization of cationic drugs in lung surfactant. Pharmaceutical Research. 2003; 20:11:1858–1863.
     [Google Scholar]
  19. Mansour HM, Rhee Y-S, Wu X. Nanomedicine in pulmonary delivery. International Journal of Nanomedicine. 2009; 4::299.
     [Google Scholar]
  20. Beck-Broichsitter M, Gauss J, Packhaeuser CB, Lahnstein K, Schmehl T, Seeger W, Kissel T, Gessler T. Pulmonary drug delivery with aerosolizable nanoparticles in an ex vivo lung model. International Journal of Pharmaceutics. 2009; 367:1:169–178.
     [Google Scholar]
  21. Labiris N, Dolovich M. Pulmonary drug delivery. Part I: Physiological factors affecting therapeutic effectiveness of aerosolized medications. British Journal of Clinical Pharmacology. 2003; 56:6:588–599.
     [Google Scholar]
  22. Davies C, Muir D. Deposition of inhaled particles in human lungs. Nature 1966; 211::90–91.
     [Google Scholar]
  23. Jain KK. Drug delivery systems-an overview. Drug delivery systems. Springer 2008;:1–50.
     [Google Scholar]
  24. Thulasiramaraju TV, Tejeswar Kumar B, Nikilesh Babu M. Pulmonary drug delivery systems-an overview. Asian Journal of Research in Pharmaceutical Sciences and Biotechnology. 2013;:16–34.
     [Google Scholar]
  25. Yang W, Peters JI, Williams III RO. Inhaled nanoparticles—a current review. International Journal of Pharmaceutics. 2008; 356:1:239–247.
     [Google Scholar]
  26. Boucher R. Regulation of airway surface liquid volume by human airway epithelia. Pfluegers Archiv. 2003; 445:4:495–498.
     [Google Scholar]
  27. Champion JA, Walker A, Mitragotri S. Role of particle size in phagocytosis of polymeric microspheres. Pharmaceutical Research. 2008; 25:8:1815–1821.
     [Google Scholar]
  28. Usmani OS, Biddiscombe MF, Underwood SR, Barnes PJ. Characterization of the generation of radiolabeled monodisperse albuterol particles using the spinning-top aerosol generator. Journal of Nuclear Medicine. 2004; 45:1:69–73.
     [Google Scholar]
  29. Edwards DA, Ben-Jebria A, Langer R. Recent advances in pulmonary drug delivery using large, porous inhaled particles. Journal of Applied Physiology. 1998; 85:2:379–385.
     [Google Scholar]
  30. Ehrhardt C, Fiegel J, Fuchs S, Abu-Dahab R, Schaefer U, Hanes J, Lehr CM. Drug absorption by the respiratory mucosa: Cell culture models and particulate drug carriers. Journal of Aerosol Medicine. 2002; 15:2:131–139.
     [Google Scholar]
  31. Tsapis N, Bennett D, Jackson B, Weitz DA, Edwards D. Trojan particles: Large porous carriers of nanoparticles for drug delivery. Proceedings of the National Academy of Sciences. 2002; 99:19:12001–12005.
     [Google Scholar]
  32. El-Sherbiny IM, McGill S, Smyth HD. Swellable microparticles as carriers for sustained pulmonary drug delivery. Journal of Pharmaceutical Sciences. 2010; 99:5:2343–2356.
     [Google Scholar]
  33. El-Sherbiny IM, Smyth HD. Biodegradable nano-micro carrier systems for sustained pulmonary drug delivery:(I) Self-assembled nanoparticles encapsulated in respirable/swellable semi-IPN microspheres. International Journal of Pharmaceutics. 2010; 395:1:132–141.
     [Google Scholar]
  34. Champion JA, Mitragotri S. Role of target geometry in phagocytosis. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103:13:4930–4934.
     [Google Scholar]
  35. Champion JA, Mitragotri S. Shape induced inhibition of phagocytosis of polymer particles. Pharmaceutical Research. 2009; 26:1:244–249.
     [Google Scholar]
  36. Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nature Reviews Drug Discovery. 2003; 2:3:214–221.
     [Google Scholar]
  37. Suzuki Y, Yamaguchi T. Effects of hyaluronic acid on macrophage phagocytosis and active oxygen release. Agents and Actions. 1993; 38:1:32–37.
     [Google Scholar]
  38. Surendrakumar K, Martyn G, Hodgers E, Jansen M, Blair J. Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs. Journal of Controlled Release. 2003; 91:3:385–394.
     [Google Scholar]
  39. Evora C, Soriano I, Rogers RA, Shakesheff KM, Hanes J, Langer R. Relating the phagocytosis of microparticles by alveolar macrophages to surface chemistry: The effect of 1, 2-dipalmitoylphosphatidylcholine. Journal of Controlled Release. 1998; 51:2:143–152.
     [Google Scholar]
  40. Hickey AJ. Pharmaceutical inhalation aerosol technology. CRC Press 2003.
     [Google Scholar]
  41. Niven RW, Whitcomb KL, Shaner L, Ip AY, Kinstler OB. The pulmonary absorption of aerosolized and intratracheally instilled rhG-CSF and monoPEGylated rhG-CSF. Pharmaceutical Research. 1995; 12:9:1343–1349.
     [Google Scholar]
  42. Meenach SA, Vogt FG, Anderson KW, Hilt JZ, McGarry RC, Mansour HM. Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly (ethylene glycol)(DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols. International Journal of Nanomedicine. 2013; 8::275.
     [Google Scholar]
  43. Jaafar-Maalej C, Elaissari A, Fessi H. Lipid-based carriers: Manufacturing and applications for pulmonary route. Expert Opinion on Drug Delivery. 2012; 9:9:1111–1127.
     [Google Scholar]
  44. Lasic DD. Liposomes in gene delivery. CRC press 1997.
     [Google Scholar]
  45. Bai S, Gupta V, Ahsan F. Cationic liposomes as carriers for aerosolized formulations of an anionic drug: Safety and efficacy study. European Journal of Pharmaceutical Sciences. 2009; 38:2:165–171.
     [Google Scholar]
  46. Kaur G, Narang R, Rath G, Goyal AK. Advances in pulmonary delivery of nanoparticles. Artificial Cells, Blood Substitutes and Biotechnology. 2012; 40:1-2:75–96.
     [Google Scholar]
  47. Schreier H, Gonzalez-Rothi RJ, Stecenko AA. Pulmonary delivery of liposomes. Journal of Controlled Release. 1993; 24:1:209–223.
     [Google Scholar]
  48. Saari SM, Vidgren MT, Koskinen MO, Turjanmaa ViM, Waldrep JC, Nieminen MM. Regional lung deposition and clearance of 99mTc-labeled beclomethasone-DLPC liposomes in mild and severe asthma. CHEST Journal. 1998; 113:6:1573–1579.
     [Google Scholar]
  49. Arppe J, Vidgren M, Waldrep J. Pulmonary pharmacokinetics of cyclosporin A liposomes. International Journal of Pharmaceutics. 1998; 161:2:205–214.
     [Google Scholar]
  50. Poyner E, Alpar H, Almeida A, Gamble M, Brown M. A comparative study on the pulmonary delivery of tobramycin encapsulated into liposomes and PLA microspheres following intravenous and endotracheal delivery. Journal of Controlled Release. 1995; 35:1:41–48.
     [Google Scholar]
  51. Gibbons AM, McElvaney NG, Taggart CC, Cryan S-A. Delivery of rSLPI in a liposomal carrier for inhalation provides protection against cathepsin L degradation. Journal of Microencapsulation. 2009; 26:6:513–522.
     [Google Scholar]
  52. Shahiwala A, Misra A. Pulmonary absorption of liposomal levonorgestrel. AAPS PharmSciTech. 2004; 5:1:96–100.
     [Google Scholar]
  53. Nag OK, Awasthi V. Surface engineering of liposomes for stealth behavior. Pharmaceutics. 2013; 5:4:542–569.
     [Google Scholar]
  54. Beck-Broichsitter M, Ruppert C, Schmehl T, Guenther A, Betz T, Bakowsky U, Seeger W, Kissel T, Gessler T. Biophysical investigation of pulmonary surfactant surface properties upon contact with polymeric nanoparticles in vitro. Nanomedicine: Nanotechnology, Biology and Medicine. 2011; 7:3:341–350.
     [Google Scholar]
  55. Nassimi M, Schleh C, Lauenstein H, Hussein R, Hoymann H, Koch W, Pohlmann G, Krug N, Sewald K, Rittinghausen S, Braun A, Müller-Goymann C. A toxicological evaluation of inhaled solid lipid nanoparticles used as a potential drug delivery system for the lung. European Journal of Pharmaceutics and Biopharmaceutics. 2010; 75:2:107–116.
     [Google Scholar]
  56. Nassimi M, Schleh C, Lauenstein H-D, Hussein R, Lübbers K, Pohlmann G, Switalla S, Sewald K, Müller M, Krug N, Müller-Goymann CC, Braun A. Low cytotoxicity of solid lipid nanoparticles in in vitro and ex vivo lung models. Inhalation Toxicology. 2009; 21:S1:104–109.
     [Google Scholar]
  57. Liu J, Gong T, Fu H, Wang C, Wang X, Chen Q, Zhang Q, He Q, Zhang Z. Solid lipid nanoparticles for pulmonary delivery of insulin. International Journal of Pharmaceutics. 2008; 356:1:333–344.
     [Google Scholar]
  58. Yang W, Tam J, Miller DA, Zhou J, McConville JT, Johnston KP, Williams RO 3rd. High bioavailability from nebulized itraconazole nanoparticle dispersions with biocompatible stabilizers. International Journal of Pharmaceutics. 2008; 361:1:177–188.
     [Google Scholar]
  59. MuÈller RH, MaÈder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery–a review of the state of the art. European Journal of Pharmaceutics and Biopharmaceutics. 2000; 50:1:161–177.
     [Google Scholar]
  60. Li Y-Z, Sun X, Gong T, Liu J, Zuo J, Zhang Z-R. Inhalable microparticles as carriers for pulmonary delivery of thymopentin-loaded solid lipid nanoparticles. Pharmaceutical Research. 2010; 27:9:1977–1986.
     [Google Scholar]
  61. Weber S, Zimmer A, Pardeike J. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for pulmonary application: A review of the state of the art. European Journal of Pharmaceutics and Biopharmaceutics. 2014; 86:1:7–22.
     [Google Scholar]
  62. Illum L, Watts PJ. Polysaccharide microspheres for the pulmonary delivery of drugs. Google Patents 1997.
     [Google Scholar]
  63. Feng S-S, Chien S. Chemotherapeutic engineering: Application and further development of chemical engineering principles for chemotherapy of cancer and other diseases. Chemical Engineering Science. 2003; 58:18:4087–4114.
     [Google Scholar]
  64. Williams III RO, Barron MK, José Alonso M, Remuñán-López C. Investigation of a pMDI system containing chitosan microspheres and P134a. International Journal of Pharmaceutics. 1998; 174:1:209–222.
     [Google Scholar]
  65. Wang H, Xu Y, Zhou X. Docetaxel-loaded chitosan microspheres as a lung targeted drug delivery system: In vitro and in vivo evaluation. International Journal of Molecular Sciences. 2014; 15:3:3519–3532.
     [Google Scholar]
  66. Doan T, Olivier J. Preparation of rifampicin-loaded PLGA microspheres for lung delivery as aerosol by premix membrane homogenization. International Journal of Pharmaceutics. 2009; 382:1:61–66.
     [Google Scholar]
  67. Grenha A, Grainger CI, Dailey LA, Seijo B, Martin GP, Remuñán-López C, Forbes B. Chitosan nanoparticles are compatible with respiratory epithelial cells in vitro. European Journal of Pharmaceutical Sciences. 2007; 31:2:73–84.
     [Google Scholar]
  68. Kaye RS, Purewal TS, Alpar HO. Simultaneously manufactured nano-in-micro (SIMANIM) particles for dry-powder modified-release delivery of antibodies. Journal of Pharmaceutical Sciences. 2009; 98:11:4055–4068.
     [Google Scholar]
  69. Marsh D, Bartucci R, Sportelli L. Lipid membranes with grafted polymers: Physicochemical aspects. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2003; 1615:1:33–59.
     [Google Scholar]
  70. Davidsen J, Vermehren C, Frokjaer S, Mouritsen OG, Jørgensen K. Drug delivery by phospholipase A2 degradable liposomes. International Journal of Pharmaceutics. 2001; 214:1:67–69.
     [Google Scholar]
  71. Lavasanifar A, Samuel J, Kwon GS. Poly (ethylene oxide)-block-poly (l-amino acid) micelles for drug delivery. Advanced Drug Delivery Reviews. 2002; 54:2:169–190.
     [Google Scholar]
  72. Gaber NN, Darwis Y, Peh K-K, Tan YT-F. Characterization of polymeric micelles for pulmonary delivery of beclomethasone dipropionate. Journal of Nanoscience and Nanotechnology. 2006; 6:9-10:3095–3101.
     [Google Scholar]
  73. Duchêne D, Ponchel G, Wouessidjewe D. Cyclodextrins in targeting: Application to nanoparticles. Advanced Drug Delivery Reviews. 1999; 36:1:29–40.
     [Google Scholar]
  74. Duchene D, Wouessidjewe D, Ponchel G. Cyclodextrins and carrier systems. Journal of Controlled Release. 1999; 62:1:263–268.
     [Google Scholar]
  75. Yang W, Chow KT, Lang B, Wiederhold NP, Johnston KP, Williams III RO. In vitro characterization and pharmacokinetics in mice following pulmonary delivery of itraconazole as cyclodextrin solubilized solution. European Journal of Pharmaceutical Sciences. 2010; 39:5:336–347.
     [Google Scholar]
  76. Tolman JA, Nelson NA, Son YJ, Bosselmann S, Wiederhold NP, Peters JI, McConville JT, Williams RO 3rd. Characterization and pharmacokinetic analysis of aerosolized aqueous voriconazole solution. European Journal of Pharmaceutics and Biopharmaceutics. 2009; 72:1:199–205.
     [Google Scholar]
  77. Ungaro F, d'Emmanuele di Villa Bianca R, Giovino C, Miro A, Sorrentino R, Quaglia F, La Rotonda MI. Insulin-loaded PLGA/cyclodextrin large porous particles with improved aerosolization properties: In vivo deposition and hypoglycaemic activity after delivery to rat lungs. Journal of Controlled Release. 2009; 135:1:25–34.
     [Google Scholar]
  78. Jalalipour M, Najafabadi AR, Gilani K, Esmaily H, Tajerzadeh H. Effect of dimethyl-β-cyclodextrin concentrations on the pulmonary delivery of recombinant human growth hormone dry powder in rats. Journal of Pharmaceutical Sciences. 2008; 97:12:5176–5185.
     [Google Scholar]
  79. Makino K. Pulmonary drug delivery system. [Available from: http://www.tus.ac.jp/rist/lab/introduction/2research-centers/906.html .
     [Google Scholar]
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Inhaled nano- and microparticles for drug delivery
Global Cardiology Science and Practice 2015, 2 (2015); https://doi.org/10.5339/gcsp.2015.2
/content/journals/10.5339/gcsp.2015.2
/content/journals/10.5339/gcsp.2015.2
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  • Article Type: Review Article
Keyword(s): bioavailability, liposomes, micelles, particulate-based drug delivery system, polymeric micro/nanoparticles, pulmonary clearance mechanisms, pulmonary delivery and solid lipid nanoparticles
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