Effect of preparation conditions on morphology and release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion method

Yi Yan Yang*, Tai Shung Chung, Xin Lai Bai, Woon Khiong Chan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

277 Scopus citations

Abstract

We have investigated the key parameters to fabricate PDLLA (Poly(DL-lactic acid)), PDLLGA (Poly(DL-lactic-co-glycolic acid) 65:35 and blends of PDLLGA 65:35 and PEG (Poly(ethylene glycol)) microspheres containing bovine serum albumin (BSA) as a model protein using the double-emulsion (water-in-oil-in-water) solvent extraction/evaporation method. The release profiles of microspheres were investigated at 22°C in order to develop controlled release devices for marine fishes in tropical area. Various factors that influence the size of microspheres, encapsulation efficiency, initial release, morphology and release profiles of microspheres, and BSA distribution within microspheres have been investigated. These factors include preparation temperature, solvent removal rate, volume ratio of oil phase to internal water phase, and polymer concentration. Microspheres fabricated at a low volume ratio of oil phase to internal water phase and a low polymer concentration tend to have a large surface area, a low bulk density, resulting in a high initial burst and a fast release of BSA. Fabrication temperature heavily affects solvent extraction/evaporation and mechanism of phase-inversion. The microspheres fabricated at 4 and 38°C yield the highest encapsulation efficiency (52.0-48.0%) and lowest initial BSA release (18.8-20.0%), while microspheres produced at 22°C have the lowest encapsulation efficiency and highest initial burst. This interesting phenomenon is due to the fact that different phase-inversion paths occur when preparation temperature varies. Nucleation growth and spinodal decomposition dominate the skin formation at low preparation temperatures, while evaporation-driven skin formation takes place at high preparation temperatures. The relationship between the release profile and the rate of continuous water-phase addition is extremely complicated. Slow demixing dominates the interface skin formation at low continuous water-phase addition rates and results in fine porous skin structure, while rapid demixing dominates at high continuous water-phase addition rates and also leads to microspheres with a porous skin. Thus both have high initial bursts and fast release rates. A continuous water-phase addition of 3 ml/min may yield the microspheres having a low initial burst and a slow release rate. (C) 2000 Elsevier Science Ltd. All rights reserved.

Original languageEnglish (US)
Pages (from-to)2223-2236
Number of pages14
JournalCHEMICAL ENGINEERING SCIENCE
Volume55
Issue number12
DOIs
StatePublished - Jun 2000
Externally publishedYes

Keywords

  • In vitro release profiles
  • Microspheres
  • Morphology
  • Poly(DL-lactic acid)
  • Poly(DL-lactic-co-glycolic acid)

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering
  • Industrial and Manufacturing Engineering

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