Skip to main content
SpringerLink
Log in

Controlled release of dexamethasone from PLGA microspheres embedded within polyacid-containing PVA hydrogels

  • Published:
The AAPS Journal Aims and scope Submit manuscript

Abstract

The development of zero-order release systems capable of delivering drug(s) over extended periods of time is deemed necessary for a variety of biomedical applications. We hereby describe a simple, yet versatile, delivery platform based on physically cross-linked poly(vinyl alcohol) (PVA) microgels (cross-linked via repetitive freeze/thaw cycling) containing entrapped dexamethasone-loaded poly(lacticco-glycolic acid) (PLGA) microspheres for controlled delivery over a 1-month period. The incorporation of polyacids, such as humic acids, Nafion, and poly(acrylic acid), was found to be crucial for attaining approximately zero-order release kinetics, releasing 60% to 75% of dexamethasone within 1 month. Microspheres alone entrapped in the PVA hydrogel resulted in negligible drug release during the 1-month period of investigation. On the basis of a comprehensive evaluation of the structure-property relationships of these hydrogel/microsphere composites, in conjunction with their in vitro release performance, it was concluded that these polyacids segregate on the PLGA microsphere surfaces and thereby result in localized acidity. These surface-associated polyacids appear to cause acid-assisted hydrolysis to occur from the surface inwards. Such systems show potential for a variety of localized controlled drug delivery applications such as coatings for implantable devices.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hassan CM, Peppas NA. Structure and applications of poly(vinyl alcohol) hydrogels produced by conventional cross-linking or by freezing/thawing methods.Adv Polym Sci. 2000;153:37–65.

    Article  CAS  Google Scholar 

  2. Hassan CM, Stewart JE, Peppas NA. Diffusional characteristics of freeze/thawed poly(vinyl alcohol) hydrogels: applications to protein controlled release from multilaminate devices.Eur J Pharm Biopharm. 2000;49:161–165.

    Article  PubMed  CAS  Google Scholar 

  3. Cascone MG, Zhu Z, Borselli F, Lazzeri L. Poly(vinyl alcohol) hydrogels as hydrophilic matrices for the release of lipophilic drugs loaded in PLGA nanoparticles.J Mater Sci Mater Med. 2002;13:29–32.

    Article  CAS  Google Scholar 

  4. Peppas NA, Merrill EW. Differential scanning calorimetry of crystallized PVA hydrogels.J Appl Polym Sci. 1976;20:1457–1465.

    Article  CAS  Google Scholar 

  5. Peppas NA, Merrill EW. Determination of interaction parameter γ 1 for PVA and water in gels cross-linked from solutions.J Polym Sci Polym Chem Ed. 1976;14:441–464.

    Article  CAS  Google Scholar 

  6. Danno A. Gel formation of aqueous solutions of poly(vinyl alcohol) irradiated with a cobalt-60 source.J Phys Soc Jpn. 1958;13:722–727.

    Article  CAS  Google Scholar 

  7. Yokoyama F, Masada I, Shimamura K, Ikawa T, Monobe K. Morphology and structure of highly elastic poly(vinyl alcohol) hydrogel prepared by repeated freezing and melting.Coll Polym Sci. 1986;264:595–601.

    Article  CAS  Google Scholar 

  8. Lozinsky VI. Cryotropic gelation of poly(vinyl alcohol) solutions.Russ Chem Rev. 1998;67:573–586.

    Article  Google Scholar 

  9. Tamura K, Nakamura T, Okada K. New hydrogel from poly(vinyl alcohol) and its fundamental study for medical applications.Jap J Artif Organs. 1984;13:1197–1201.

    Google Scholar 

  10. Tamura K, Ike O, Hitomi S, Isobe J, Shmizu Y, Nambu M. A new hydrogel and its medical application.Trans Am Soc Artif Intern Organs. 1986;32:605–608.

    CAS  Google Scholar 

  11. Stauffer SR, Peppas NA. Poly(vinyl alcohol) hydrogels prepared by freezing-thawing cycling processing.Polym. 1992;33:3932–3936.

    Article  CAS  Google Scholar 

  12. Lozinsky VI, Vainerman ES, Domotenko LV, et al. Study of cryostructurization of polymer systems. VII. Structure formation under freezing of poly(vinyl alcohol) aqueous solutions.Coll Polym Sci. 1986;264:19–24.

    Article  CAS  Google Scholar 

  13. Bao QB, McCullen GM, Higham PA, Dumbleton JH, Yuan HA. The artificial disc: theory, design and materials.Biomaterials. 1996;17:1157–67.

    Article  PubMed  CAS  Google Scholar 

  14. Ushijima M, Oka M, Hyon S-H, et al. Study on the improvement of wear-resistant properties of artificial articular cartilage.Seitai Zairyo. 1996;14:201–204.

    CAS  Google Scholar 

  15. Oka M, Ushio K, Kumar P, et al. Development of artificial articular cartilage.Proc Inst Mech Eng [H]. 2000;214:59–68.

    CAS  Google Scholar 

  16. Kuriaki M, Nakamura K, Mizutani J. Application of transparent poly(vinyl alcohol) gel to contact lens.Kobunshi Ronbunshu. 1989;46:739–743.

    CAS  Google Scholar 

  17. Lozinsky VI, Zubov AL, Titova EF. Poly(vinyl alcohol) cryogels employed as matrices for cell immobilization. 2. Entrapped cells resemble porous fillers in their effects on the properties of PVA-cryogel carrier.Enzyme Microb Technol. 1997;20:182–190.

    Article  CAS  Google Scholar 

  18. Lozinsky VI, Plieva FM. Poly(vinyl alcohol) cryogels employed as matrices for cell immobilization. 3. Overview of recent research and developments.Enzyme Microb Technol. 1998;23:227–242.

    Article  CAS  Google Scholar 

  19. Mongia NK, Anseth KS, Peppas NA. Mucoadhesive poly(vinyl alcohol) hydrogels produced by freezing/thawing processes: applications in the development of wound healing systems.J Biomater Sci Polym Ed. 1996;7:1055–1064.

    PubMed  CAS  Google Scholar 

  20. Peppas NA, Mongia NK. Ultrapure poly(vinyl alcohol) hydrogels with mucoadhesive drug delivery characteristics.Eur J Pharm Biopharm. 1997;43:51–58.

    Article  CAS  Google Scholar 

  21. Takamura A, Ishii F, Hidaka H. Drug release from poly(vinyl alcohol) gel prepared by freeze-thaw procedure.J Control Release. 1992;20:21–27.

    Article  CAS  Google Scholar 

  22. Patil SD, Papadimitrakopoulos F, Burgess DJ. Dexamethasone-loaded PLGA Micropheres/PVA Hydrogel Composites for Inflammation Control.Diabetes Technology and Therapeutics. 2004;6:887–897.

    Article  PubMed  CAS  Google Scholar 

  23. Bourke SL, Al-Khalili M, Briggs T, Michniak BB, Kohn J, Poole-Warren LA. A photo-crosslinked poly(vinyl alcohol) hydrogel growth factor release vehicle for wound healing applications.AAPS PharmSci. 2003;5(4):E33.

    Article  PubMed  Google Scholar 

  24. Freiberg S, Zhu XX. Polymer microspheres for controlled drug release.Int J Pharm. 2004;282:1–18.

    Article  PubMed  CAS  Google Scholar 

  25. Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM. Polymeric Systems for Controlled Drug Release.Chem Rev. 1999;99:3181–3198.

    Article  PubMed  CAS  Google Scholar 

  26. Kim T-K, Burgess DJ. Formulation and release characteristics of poly(lactic-co-glycolic acid) microspheres containing chemically modified protein.J Pharm Pharmacol. 2001;53:23–31.

    Article  PubMed  CAS  Google Scholar 

  27. Hickey T, Kreutzer D, Burgess DJ, Moussy F. Dexamethasone/PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devices.Biomaterials. 2001;23:1649–1656.

    Article  Google Scholar 

  28. Galeska I, Hickey T, Moussy F, Kreutzer D, Papadimitrakopoulos F. Characterization and biocompatibility studies of novel humic acid based films as membrane material for an implantable glucose sensor.Biomacromolecules. 2001;2:1249–1255.

    Article  PubMed  CAS  Google Scholar 

  29. Wershaw RL.Humic Substances II. In Search of Structure. New York, NY: John Wiley & Sons; 1989.

    Google Scholar 

  30. Stevenson FJ.Humus Chemistry, Genesis, Composition, Reactions. New York, NY: John Wiley & Sons; 1994.

    Google Scholar 

  31. Peppas NA, Hansen PJ. Crystallization kinetics of poly(vinyl alcohol).J Appl Polym Sci. 1982;27:4787–4797.

    Article  CAS  Google Scholar 

  32. Urushizaki F, Yamaguchi H, Nakamura K, Namajiri S, Sugibayashi K, Morimoto Y. Swelling and mechanical properties of poly(vinyl alcohol) hydrogels.Int J Pharm. 1990;58:135–142.

    Article  CAS  Google Scholar 

  33. Lozinsky VI, Zubov AL, Titova EF. Swelling behavior of poly(vinyl alcohol) cryogels employed as matrixes for cell immobilization.Enzyme Microb Technol. 1996;18:561–569.

    Article  CAS  Google Scholar 

  34. Takamura A, Ishii F. Preparation of freeze-thaw poly(vinyl alcohol) emulsion gel suppository.Yakugaku Zasshi. 1987;111:45–50.

    Google Scholar 

  35. Watase M, Nishinari K. Reological and DSC changes în poly(vinyl alcohol) gels induced by immersion in water.J Polym Sci: Polym Phys Ed. 1985;23:1803–1811.

    Article  CAS  Google Scholar 

  36. Nielsen LE, Landel RF. Particulate-filled polymers. In: Landel RF, ed.Mechanical Properties of Polymers and Composites. 2nd ed. New York, NY: Marcel Dekker; 1994;377–460.

    Google Scholar 

  37. Bucknall CB. Applications of microscopy to the deformation and fracture of rubber-toughened polymers.J Microsc. 2001;201:221–229.

    Article  PubMed  CAS  Google Scholar 

  38. Yamada H.Strength of Biological Tissues. Baltimore, MD: Williams & Wilkins, 1970.

    Google Scholar 

  39. Vert M, Li S, Garreau H, et al. Complexity of the hydrolytic degradation of aliphatic polyesters.Angew Makromol Chem. 1997;247:239–253.

    Article  CAS  Google Scholar 

  40. Li SM, Garreau M, Vert H. Structure-property relationships in the case of the degradation of massive aliphatic poly-(a-hydroxy acids) in aqueous media, part 1: poly(DL-lactic acid).J Mater Sci Mater Med. 1990;1:123–130.

    Article  CAS  Google Scholar 

  41. Li SM, Garreau H, Vert M. Structure-property relationships in the case of the degradation of massive poly(a-hydroxy acids) in aqueous media. Part 2. Degradation of lactide-glycolide copolymers: PLA37.5GA25 and PLA75GA25.J Mater Sci Mater Med. 1990;1:131–139.

    Article  CAS  Google Scholar 

  42. Fu K, Pack DW, Klibanov AM, Langer R. Visual evidence of acidic environment within degrading poly(lactic-co-glycolic acid) (PLGA) microspheres.Pharm Res. 2000;17:100–106.

    Article  PubMed  CAS  Google Scholar 

  43. Gierke TD, Hsu WY. Perfluorinated ion exchange membranes. In: Yeager HL.Perfluorinated Ionomer Membranes. Washington, DC: American Chemical Society 1982;283–307.

    Google Scholar 

  44. Kozlov M, Quarmyne M, Chen W, McCarthy TJ. Adsorption of Poly(vinyl alcohol) to Hydrophobic Substrates: A General Approach for Hydrophilizing and Chemically Activating Surfaces.Macromolecules. 2003;36:6054–6059.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nanomaterials Optoelectronic Laboratory, Department of Chemistry, Polymer Program, Institute of Materials Science, University of Connecticut, 97 N Eagleville Road, 06269, Storrs, CT

    Izabela Galeska, Debjit Chatttopadhyay & Fotios Papadimitrakopoulos

  2. Department of Pharmaceutical Sciences, University of Connecticut, 372 Fairfield Way, 06269, Storrs, CT

    Tae-Kyoung Kim, Siddhesh D. Patil, Upkar Bhardwaj & Diane J. Burgess

Authors
  1. Izabela Galeska
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tae-Kyoung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siddhesh D. Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Upkar Bhardwaj
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Debjit Chatttopadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fotios Papadimitrakopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Diane J. Burgess
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Diane J. Burgess.

Additional information

Published: September 2, 2005

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galeska, I., Kim, TK., Patil, S.D. et al. Controlled release of dexamethasone from PLGA microspheres embedded within polyacid-containing PVA hydrogels. AAPS J 7, 22 (2005). https://doi.org/10.1208/aapsj070122

Download citation

  • Received:

  • Accepted:

  • DOI: https://doi.org/10.1208/aapsj070122

Keywords

Search

Navigation