POE-PEG-POE triblock copolymeric microspheres containing protein - I. Preparation and characterization

Poly(ortho ester) (POE)-poly (ethylene glycol) (PEG) triblock copolymers (P OE-PEG-POE) with different PEG contents were synthesised as carriers for co ntrolled protein delivery. POE-PEG-POE microspheres containing bovine serum albumin (BSA) were prepared using a double-emulsion (water-in-oil-in-water ) Process. In this first paper of a two-part series, we report the fundamen tals of the fabrication and characterization of POE-PEG-POE microspheres. B ecause the triblock copolymer is more hydrophilic than neat poly(ortho este r), the triblock copolymer yields a more stable first emulsion (water-in-oi l) and a greater BSA encapsulation efficiency (90% vs. 30%). No BSA is foun d on POE-PEG-POE microsphere surfaces measured by X-ray photoelectron spect roscopy, while uniform BSA distributions are observed within the microspher es by confocal microscopy. SEM pictures show that an increase in PEG conten t results in microspheres with a denser cross-section because of a more sta ble first emulsion and better affinity between the copolymer and water. POE -PEG(20%)-POE suffers significant swelling during the fabrication process a nd yields the biggest microspheres. However, the POE-PEG(30%)-POE microsphe res are much smaller since the dissolution loss of POE-PEG(30%)-POE in the external water phase may be much higher than that of POE-PEG(20%)-POE. The salt concentration in the external water phase significantly affects the mo rphology of the resultant microspheres. Microspheres with a dense wall are produced when using pure water as the external water phase. Polymer concent ration has less impact on BSA encapsulation efficiency but has a considerab le effect on microsphere size and morphology. Increasing the concentration of the polyvinyl alcohol emulsifier does not cause an obvious decrease in m icrosphere size. However, increased BSA loading results in bigger microsphe res. (C) 2001 Elsevier Science BY. All rights reserved.