Control of protein delivery from amphiphilic poly(ether ester) multiblock copolymers by varying their water content using emulsification techniques

J.M. Bezemer, D.W. Grijpma, P.J. Dijkstra, C.A. van Blitterswijk, J. Feijen

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

Protein-containing films and microspheres, based on poly(ethylene glycol)–poly(butylene terephthalate) (PEG–PBT) multiblock copolymers, were prepared from water-in-oil (w/o) emulsions. The properties of the matrices could be controlled by the water-to-polymer ratio (w/p) in the w/o emulsion. A linear increase in water uptake of the matrices was observed with increasing emulsion w/p. This could be explained by an increase in the number of dispersed water-rich domains in the polymer matrix. At low volume fraction of the dispersed phase (ε), lysozyme release was mainly dependent on the permeability of the swollen polymer bulk. Above a critical volume fraction (the percolation threshold εc), the dispersed water-rich phase formed an interconnected network, which largely enhanced the permeability of the matrix. Determination of the permeability of PEG–PBT matrices for vitamin B12 as a function of ε confirmed the formation of such an interconnected network. This interconnected network could be used to achieve controlled release of a large protein (bovine serum albumin, BSA) from PEG–PBT films and microspheres. Due to its hydrodynamic diameter, BSA was screened by the polymer network when ε was low. However above εc, the fraction released BSA increased with increasing volume fraction of the dispersed phase. A very rapid BSA release could be obtained, with the majority of the incorporated BSA released within 1 day, as well as a slow and continuous release, lasting for over 150 days. When BSA-containing microspheres were prepared with a volume fraction just below the percolation threshold, a delayed release was observed. This was attributed to the effect of polymer degradation on matrix permeability.
Original languageEnglish
Pages (from-to)307-320
JournalJournal of controlled release
Volume66
Issue number2-3
DOIs
Publication statusPublished - 2000

Keywords

  • Block copolymer
  • Heterogeneous network
  • Percolation
  • Permeability
  • Protein release

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