Controlled protein delivery from biodegradable tyrosine-containing poly(anhydride-co-imide) microspheres

Masatoshi Chiba, Justin Hanes, Robert Langer

Research output: Contribution to journalArticle

Abstract

Polymer microspheres capable of the controlled release of macromolecules for periods ranging from days to over a month were developed. The microspheres were made using a new family of anhydride polymers: tyrosine-containing poly(anhydride-co-imides), specifically poly[trimellitylimido-L-tyrosine-co-sebacic acid-co-1,3-bis(carboxyphenoxy)propane] anhydrides [poly(TMA-Tyr:SA:CPP)]. These polymers may be of particular interest for controlled delivery of vaccine antigens due to the incorporation of an immunological adjuvant, L-tyrosine, into their backbone. Microspheres were produced from a variety of polymer compositions using a double-emulsion solvent-evaporation technique, and tested for their ability to provide controlled release of a model protein, bovine serum albumin, in vitro. The microspheres are spherical with smooth surfaces and encapsulate greater than 70% of the protein. Protein release rates from polymers of identical composition could be varied from 0.3 to over 125 μg per mg spheres per month by changing the amount of protein encapsulated. This effect can be magnified by using polymers with various monomer ratios. A close correlation between protein release and polymer weight loss was observed, suggesting a release mechanism controlled mainly by polymer erosion. Bovine serum albumin release from poly(TMA-Tyr:SA:CPP) microspheres is also pH sensitive, being enhanced at high pH and depressed under acidic conditions.

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalBiomaterials
Volume18
Issue number13
DOIs
StatePublished - Jul 1 1997
Externally publishedYes

Keywords

  • Biodegradable
  • Polyanhydride
  • Polymer microspheres
  • Protein delivery
  • Vaccines

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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