Development of biodegradable poly(propylene fumarate)/poly(lactic-co- glycolic acid) blend microspheres. II. Controlled drug release and microsphere degradation

Diederik H.R. Kempen, Lichun Lu, Xun Zhu, Choll Kim, Esmaiel Jabbari, Wouter J.A. Dhert, Bradford L. Currier, Michael J. Yaszemski

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

This article describes the effects of six processing parameters on the release kinetics of a model drug Texas red dextran (TRD) from poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres as well as the degradation of these microspheres. The microspheres were fabricated using a double emulsion-solvent extraction technique in which the following six parameters were varied: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) in the internal aqueous phase, and poly-(vinyl alcohol) concentration in the external aqueous phase. We have previously characterized these microspheres in terms of microsphere morphology, size distribution, and TRD entrapment efficiency. In this work, the TRD release profiles in phosphate-buffered saline were determined and all formulations showed an initial burst release in the first 2 days followed by a decreased sustained release over a 38-day period. The initial burst release varied from 5.1 (±1.1) to 67.7 (±3.4)% of the entrapped TRD, and was affected most by the viscosity of the polymer solution used for microsphere fabrication. The sustained release between day 2 and day 38 ranged from 7.9 (±0.8) to 27.2 (±3.1)% of the entrapped TRD. During 11 weeks of in vitro degradation, the mass of the microspheres remained relatively constant for the first 3 weeks after which it decreased dramatically, whereas the molecular weight of the polymers decreased immediately upon placement in phosphate-buffered saline. Increasing the PPF content in the PPF/PLGA blend resulted in slower microsphere degradation. Overall, this study provides further understanding of the effects of various processing parameters on the release kinetics from PPF/PLGA blend microspheres thus allowing modulation of drug release to achieve a wide spectrum of release profiles.

Original languageEnglish (US)
Pages (from-to)293-302
Number of pages10
JournalJournal of Biomedical Materials Research - Part A
Volume70
Issue number2
DOIs
StatePublished - Aug 1 2004

Keywords

  • Biodegradable polymers
  • Blend microspheres
  • Controlled release
  • Drug delivery
  • Microsphere degradation
  • Poly(lactic-co-glycolic acid) (PLGA)
  • Poly(propylene fumarate) (PPF)

ASJC Scopus subject areas

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

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