Auto-catalyzed poly(ortho ester) microspheres: A study of their erosion and drug release mechanism

Hui Hui Chia, Yi Yan Yang, Tai Shung Chung*, Steve Ng, Jorge Heller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


A study has been carried out to investigate the degradation and protein release mechanisms of BSA-loaded microspheres made with auto-catalyzed poly(ortho esters) (POEs) of varying diol composition and molecular weights. Due to the instability of the POE/dichloromethane primary emulsion, microspheres made using the W/O/W double emulsion solvent extraction/evaporation method showed a multivesicular internal structure. An O/W single emulsion process yielded dense POE microspheres. Using electron scanning microscopy, the microspheres were observed to erode throughout their matrices with increasing internal pore sizes and a steady loss of mass. However, despite a substantial weight loss of almost 80% after an in vitro period of 129 days, the molecular weight of the polymer remained relatively unchanged with loss averaging about 18 and 32% for low- and high-molecular-weight POEs, respectively. Such constancy in molecular weight was similarly reflected in the glass transition temperature of the degrading microspheres. The differences in both the molecular weight loss and polydispersity index changes depended largely on the molecular weight of the polymer. For protein release of POE microspheres, an induction period followed by BSA release for a period of 3 to 10 days was observed. The lag time depended on the hydrophilicity and the molecular weight of the polymer as well as the morphology of the microspheres. Protein release was incomplete, possibly due to the slow degradation of the POE polymers, protein aggregation and protein degradation.

Original languageEnglish (US)
Pages (from-to)11-25
Number of pages15
JournalJournal of Controlled Release
Issue number1-2
StatePublished - Jul 10 2001
Externally publishedYes


  • Bovine serum albumin
  • Microspheres
  • Poly(ortho esters)
  • Release profile
  • Surface erosion

ASJC Scopus subject areas

  • Pharmaceutical Science


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