Polymers for Pulmonary Drug Delivery

  • Poonam Sheth
  • Paul B. MyrdalEmail author
Part of the Advances in Delivery Science and Technology book series (ADST)


One method by which to modify the release rate of a drug in the pulmonary tract, is through the use of polymeric systems. There are several natural and synthetic polymers that have been studied in vitro or in vivo in animals to assess pulmonary drug delivery and sustained release. This chapter focuses on some of the more common non-conjugated polymers utilized for inhalation drug delivery and draws examples from an array of pre-clinical findings.


Inhalation Polymers Sustained release 


  1. 1.
    Adi H, Young PM, Chan H, Salama R, Traini D (2010) Controlled release antibiotics for dry powder lung delivery. Drug Dev Ind Pharm 36:119–126CrossRefGoogle Scholar
  2. 2.
    Alhusban FA, Seville PC (2009) Carbomer-modified spray-dried respirable powders for pulmonary delivery of salbutamol sulfate. J Microencapsul 26:444–455PubMedCrossRefGoogle Scholar
  3. 3.
    Amecke B, Bendix D, Entenmann G (1992) Resorbable polyesters: composition, properties, and applications. Clin Mater 10:47–50PubMedCrossRefGoogle Scholar
  4. 4.
    Arnold MM, Gorman EM, Schieber LJ, Munson EJ, Berkland C (2007) NanoCipro encapsulation in monodisperse large porous PLGA microparticle. J Control Release 121:100–109PubMedCrossRefGoogle Scholar
  5. 5.
    Bailey MM, Berkland CJ (2009) Nanoparticle formulations in pulmonary drug delivery. Med Res Rev 29:196–212PubMedCrossRefGoogle Scholar
  6. 6.
    Brannon-Peppas L (1997) Polymers in controlled drug delivery. Med Plast Biomater 4:34–44Google Scholar
  7. 7.
    Cook RO, Pannu RK, Kellaway IW (2005) Novel sustained release microspheres for pulmonary drug delivery. J Control Release 104:79–90PubMedCrossRefGoogle Scholar
  8. 8.
    Coowanitwong I, Arya V, Kulvanich P, Hochhaus G (2008) Slow release formulations of inhaled rifampin. AAPS J 10:342–348PubMedCrossRefGoogle Scholar
  9. 9.
    Courrier HM, Butz N, Vandamme TF (2002) Pulmonary drug delivery systems: recent development and prospectives. Crit Rev Therap Drug Carrier Syst 19:425–498CrossRefGoogle Scholar
  10. 10.
    Donovan M, McGill S, Smyth H (2008) Swellable particles for sustained release drug delivery to the lungs. Respir Drug Deliv 3:857–860Google Scholar
  11. 11.
    Edwards DA, Ben-Jebria A, Langer R (1998) Recent advances in pulmonary drug delivery using large, porous inhaled particles. J Appl Physiol 85:379–385PubMedGoogle Scholar
  12. 12.
    Edwards DA, Hanes J, Caponetti G, Hrkach K, Ben-Jebria A, Eskew ML, Mintzes J, Deaver D, Lotan N, Langer R (1997) Large porous particles for pulmonary drug delivery. Science 276:1868–1871PubMedCrossRefGoogle Scholar
  13. 13.
    El-Baseir MM, Kellaway IW (1998) Poly(L-lactic acid) microspheres for pulmonary drug delivery: release kinetics and aerosolization studies. Int J Pharm 175:135–145PubMedCrossRefGoogle Scholar
  14. 14.
    Fu J, Fiegel J, Hanes J (2004) Synthesis and characterization of PEG-based ether anhydride terpolymers: novel polymers for controlled drug release. Macromolecules 37:7174–7180CrossRefGoogle Scholar
  15. 15.
    Fu J, Fiegel J, Krauland E, Hanes J (2002) New polymeric carriers for controlled drug delivery following inhalation or injection. Biomaterials 23:4425–4433PubMedCrossRefGoogle Scholar
  16. 16.
    Garcia-Contreras L, Morçöl T, Bell SJD, Hickey AJ (2003) Evaluation of novel particles as pulmonary delivery systems for insulin in rats. AAPS Pharm Sci 5(2):article 9CrossRefGoogle Scholar
  17. 17.
    Hickey AJ, Suarez S, Bhat M, O’Hara P, Lalor CB, Atkins K, Hopfer R, McMurry DN (1998) Efficacy of rifampicin-poly(lactide-co-glycolide) microspheres in treating tuberculosis. Respir Drug Deliv VI 1:201–209Google Scholar
  18. 18.
    Jaspart S, Bertholet P, Piel G, Dogné J, Delattre L, Evrard B (2007) Solid lipid microparticles as a sustained release system for pulmonary drug delivery. Eur J Pharm Biopharm 65:47–56PubMedCrossRefGoogle Scholar
  19. 19.
    Kawashima Y, Yamamoto H, Takeuchi H, Fujioka S, Hino T (1999) Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hypoglycemic effect. J Control Release 62:279–287PubMedCrossRefGoogle Scholar
  20. 20.
    Koushik K, Dhanda DS, Cheruvu NPS, Kompella UB (2004) Pulmonary delivery of deslorelin: large-porous PLGA particles and HPβCD complexes. Pharm Res 21:1119–1126PubMedCrossRefGoogle Scholar
  21. 21.
    Leach CL, Mameister WM, Tomai MA, Hammerbeck DM, Stefely JS (2000) Oligolactic acid (OLA) biomatricies for sustained release of asthma therapeutics. Respir Drug Deliv VII 2:291–294Google Scholar
  22. 22.
    Learoyd TP, Burrows JL, French E, Seville PC (2006) Leucine-modified PLGA-based respirable spray-dried powders for sustained drug delivery. Respir Drug Deliv 2:437–440Google Scholar
  23. 23.
    Learoyd TP, Burrows JL, French E, Seville PC (2006) Sustained drug delivery from chitosan-based respirable spray-dried powders. Respir Drug Deliv 2:441–443Google Scholar
  24. 24.
    Learoyd TP, Burrows JL, French E, Seville PC (2008) Chitosan-based spray-dried respirable powders for sustained delivery of terbutaline sulfate. Eur J Pharm Biopharm 68:224–234PubMedCrossRefGoogle Scholar
  25. 25.
    Learoyd TP, Burrows JL, French E, Seville PC (2009) Sustained delivery by leucine modified chitosan spray-dried respirable powders. Int J Pharm 372:97–104PubMedCrossRefGoogle Scholar
  26. 26.
    Li FQ, Hu JH, Lu B, Yao H, Zhang WG (2001) Ciprofloxacin-loaded bovine serum albumin microspheres: Preparation and drug-release in vitro. J Microencapsul 18:825–829PubMedCrossRefGoogle Scholar
  27. 27.
    Li Z, Stefely JS (2004) Aerosol sustained release formulations with oligolactic acid (OLA). Respir Drug Deliv IX 2:321–324Google Scholar
  28. 28.
    Louey MD, Garcia-Contreras L (2004) Controlled release products for respiratory delivery. Am Pharm Rev 7:82–87Google Scholar
  29. 29.
    Lu B, Zhang Q, Yang H (2003) Lung-targeting microspheres of carboplatin. Int J Pharm 265:1–11PubMedCrossRefGoogle Scholar
  30. 30.
    Lu D, Garcia-Contreras L, Xu D, Kurtz SL, Liu J, Braunstein M, McMurray DN, Hickey AJ (2007) Poly (lactide-c-glycolide) microspheres in respirable sizes enhance an in vitro T cell response to Mycobacterium tuberculosis antigen 85B. Pharm Res 24:1834–1843PubMedCrossRefGoogle Scholar
  31. 31.
    Morimoto K, Katsumata H, Yabuta T, Iwanaga K, Kakemi M, Tabata Y, Ikada Y (2002) Gelatin microsphere as a pulmonary delivery system: evaluation of salmon calcitonin absorption. J Pharm Pharmacol 52:611–617CrossRefGoogle Scholar
  32. 32.
    Morimoto K, Metsugi K, Katsumata H, Iwanaga K, Kakemi M (2001) Effects of low-viscosity sodium hyaluronate preparation on pulmonary absorption of rh-insulin in rats. Drug Dev Ind Pharm 27:365–371PubMedCrossRefGoogle Scholar
  33. 33.
    Mu L, Feng SS (2001) Fabrication, characterization and in vitro release of paclitaxel (Taxol®) loaded poly (lactic-co-glycolic acid) microspheres prepared by pray drying technique with lipid/cholesterol emulsifiers. J Control Release 76:239–254PubMedCrossRefGoogle Scholar
  34. 34.
    Müller RH, Maaβen S, Wayhers H, Specht F, Lucks JS (1996) Cyctotoxcity of magnetite-loaded polylactide, polylactide/glycolide particles and solid lipid nanoparticles. Int J Pharm 138:85–94CrossRefGoogle Scholar
  35. 35.
    Nah J, Jeong Y, Cho C, Kim S (2000) Drug-delivery system based on core-shell type nanoparticles composed of poly(γ-benzyl-L-glutamate) and poly(ethylene oxide). J Appl Polym Sci 75:1115–1126CrossRefGoogle Scholar
  36. 36.
    Naikwade S, Bajaj A (2009) Preparation and in vitro evaluation of budesonide spray dried microparticles for pulmonary delivery. Sci Pharm 77:419–441CrossRefGoogle Scholar
  37. 37.
    Oyarzun-Ampuero FA, Brea J, Loza MI, Torres D, Alonso MJ (2009) Chitosan hyaluronic acid nanoparticles loaded with heparin for the treatment of asthma. Int J Pharm 381:122–129PubMedCrossRefGoogle Scholar
  38. 38.
    Pulapura S, Kohn J (1992) Trends in the development of bioresorbable polymers for medical applications. J Biomater Appl 6:215–250CrossRefGoogle Scholar
  39. 39.
    Rouse JJ, Whateley TL, Thomas M, Ecclecston GM (2007) Controlled drug delivery to the lungs: Influence of hyaluronic acid solution conformation on its adsorption to hydrophobic drug particles. Int J Pharm 330:175–182PubMedCrossRefGoogle Scholar
  40. 40.
    Ruan G, Feng S (2003) Preparation and characterization of poly(lactic acid) poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) microspheres for controlled release of paclitaxel. Biomaterials 24:5037–5044PubMedCrossRefGoogle Scholar
  41. 41.
    Salama RO, Traini D, Chan H, Sung A, Ammit AJ, Young PM (2009) Preparation and evaluation of controlled release microparticles for respiratory protein therapy. J Pharm Sci 98:2709–2717PubMedCrossRefGoogle Scholar
  42. 42.
    Salama R, Traini D, Chan H, Young PM (2009) Recent advances in controlled release pulmonary therapy. Curr Drug Deliv 6:404–414PubMedCrossRefGoogle Scholar
  43. 43.
    Salama RO, Traini D, Chan H, Young PM (2008) Preparation and characterisation of controlled release co-spray dried drug-polymer microparticles for inhalation 2: evaluation of in vitro release profiling methodologies for controlled release respiratory aerosols. Eur J Pharm Biopharm 70:145–152PubMedCrossRefGoogle Scholar
  44. 44.
    Schliecker G, Schmidt G, Fusch S, Wombacher R, Kissel T (2003) Hydrolytic degradation of poly(lactide-co-glycolide) films: effect of oligomers on degradation rate and crystallinity. Int J Pharm 266:39–49PubMedCrossRefGoogle Scholar
  45. 45.
    Shi S, Hickey AJ (2010) PLGA microparticles in respirable sizes enhance an in vitro T cell response to recombinant Mycobacterium tuberculosis antigen TB10.4-Ag58B. Pharm Res 27:350–360PubMedCrossRefGoogle Scholar
  46. 46.
    Shoyele SA (2008) Controlling the release of proteins/peptides via the pulmonary route. Drug Deliv Syst 437:141–148CrossRefGoogle Scholar
  47. 47.
    Suarez S, O’Hara P, Kazantseva M, Newcomer CE, Hopfer R, McMurray DN, Hickey AJ (2001) Respirable PLGA microspheres containing rifampicin for the treatment of tuberculosis: screening in an infectious disease model. Pharm Res 18:1315–1319PubMedCrossRefGoogle Scholar
  48. 48.
    Sung JC, Pulliam BL, Edwards DA (2007) Nanoparticles for drug delivery to the lungs. Trends Biotechnol 25:563–570PubMedCrossRefGoogle Scholar
  49. 49.
    Sung JC, Padilla DJ, Garcia-Contreras L, VerBerkmoes JL, Durbin D, Peloquin CA, Elbert KJ, Hickey AJ, Edwards DA (2009) Formulation and pharmacokinetics of self-assembled rifampicin nanoparticle systems for pulmonary delivery. Pharm Res 26:1847–1855PubMedCrossRefGoogle Scholar
  50. 50.
    Surendrakumar K, Martyn GP, Hodgers ECM, Jansen M, Blair JA (2003) Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery of beagle dogs. J Control Release 91:385–394PubMedCrossRefGoogle Scholar
  51. 51.
    Tahara K, Sakai T, Yamamoto H, Takeuchi H, Hirashima N, Kawashima Y (2009) Improved cellular update of chitosan-modified PLGA nanospheres by A549 cells. Int J Pharm 382:198–204PubMedCrossRefGoogle Scholar
  52. 52.
    Takeuchi H, Yamamoto H, Kawashima Y (2001) Mucoadhesive nanoparticulate systems for peptide drug delivery. Adv Drug Deliv Rev 47:39–54PubMedCrossRefGoogle Scholar
  53. 53.
    Tomoda K, Ohkoshi T, Hirota K, Sonavane GS, Nakajima T, Terada H, Komuro M, Kitazota K, Makino K (2009) Preparation and properties of inhalable nanocomposite particles for treatment of lung cancer. Colloids Surf B Biointerfaces 17:177–182CrossRefGoogle Scholar
  54. 54.
    Wang C, Muttil P, Lu D, Beltran-Torres AA, Garcia-Contreras L, Hickey AJ (2009) Screening for potential adjuvants administered by the pulmonary route for tuberculosis vaccines. AAPS J 11:139147Google Scholar
  55. 55.
    Wischke C, Schwendeman SP (2008) Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. Int J Pharm 364:298–327PubMedCrossRefGoogle Scholar
  56. 56.
    Wu L, da Rocha SRP (2007) Biocompatible and biodegradable copolymer stabilizers for hydrofluoroalkane dispersions: a colloidal probe microscopy investigation. Langmuir 23:12104–12110PubMedCrossRefGoogle Scholar
  57. 57.
    Yamada K, Kamada N, Odomi M, Okada N, Nabe T, Fujita T, Kohno S, Yamamoto A (2005) Carrageenans can regulate the pulmonary absorption of antiasthmatic drugs and their retention in the rat lung tissues without any membrane damage. Int J Pharm 293:63–72PubMedCrossRefGoogle Scholar
  58. 58.
    Yamada K (2007) Control of pulmonary absorption of drugs by various pharmaceutical excipients. Yakugaku Zasshi 127:631–641PubMedCrossRefGoogle Scholar
  59. 59.
    Yamamoto H, Kuno Y, Sugimoto S, Takeuchi H, Kawashima Y (2005) Surface modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin in mucoadhesion and opening of the intracellular tight space. J Control Release 102:373–381PubMedCrossRefGoogle Scholar
  60. 60.
    Yang Y, Bajaj N, Xu P, Ohn K, Tsifansky MD, Yeo Y (2009) Development of highly porous large PLGA microparticles for pulmonary drug delivery. Biomaterials 30:1947–1953PubMedCrossRefGoogle Scholar
  61. 61.
    Zhang Q, Shen Z, Nagai T (2001) Prolonged hypoglycemic effect of insulin-loaded polybutylcyanoacrylate nanoparticles after pulmonary administration to normal rats. Int J Pharm 218:75–80PubMedCrossRefGoogle Scholar

Copyright information

© Controlled Release Society 2011

Authors and Affiliations

  1. 1.College of PharmacyUniversity of ArizonaTucsonUSA

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