Adsorption determines in-vitro protein release rate from biodegradable microspheres: Quantitative analysis of surface area during degradation

George Crotts, Hongkee Sah, Tae Gwan Park

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121 Scopus citations

Abstract

A model protein, carboxymethylated bovine serum albumin (CM-BSA), was encapsulated within relatively fast degrading and slow degrading poly(D,L-lactide-co-glycolide, PLGA) microspheres using a multiple emulsion solvent evaporation technique. The specific surface area (σ), porosity, molecular weight change, and mass erosion of the microspheres during the degradation period were examined in relation to non-specific protein adsorption and the in-vitro protein release kinetics. Nitrogen sorption analysis of the microspheres composed of the 50/50 and 75/25 PLGA revealed that polymer degradation and subsequent mass erosion increased the specific surface area values of the microspheres by approximately 30- and 36-fold throughout 1 month and 3 months of incubation, respectively. It was found that a non-specific adsorption of encapsulated protein molecules onto the expanding polymeric surface of both microspheres severely limited the amount of protein available for release, resulting in slow and incomplete release profiles. When the protein adsorption was suppressed with the addition of 5 mM sodium dodecyl sulfate (SDS) in the release medium, a pulse-type release of the protein was exhibited from the fast degrading and slow degrading microspheres by 21 and 60 days of incubation with 65% and 77% release pulses, respectively. The onset timings of the pulsed releases in the presence of SDS corresponded well with the increases in the surface area values of degrading microspheres. This study suggests that non-specific protein adsorption is a critical factor in controlling protein release kinetics from PLGA microspheres.

Original languageEnglish
Pages (from-to)101-111
Number of pages11
JournalJournal of Controlled Release
Volume47
Issue number1
DOIs
StatePublished - 1997

Bibliographical note

Funding Information:
This work is supported in part from the Whitaker Foundation and by the Korea Science and Engineering Foundation.

Keywords

  • Poly(D,L-lactide-co-glycolide)
  • Porosity
  • Protein adsorption
  • Protein release
  • Surface area

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