Stabilization and controlled release of bovine serum albumin encapsulated in poly(D, L-lactide) and poly(ethylene glycol) microsphere blends

Purpose. The acidic microclimate in poly(D, L-lactide-co-glycolide) 50/50 m icrospheres has been previously demonstrated by our group as the primary in stability source of encapsulated bovine serum albumin (BSA). The objectives of this study were to stabilize the encapsulated model protein, BSA, and t o achieve continuous protein release by using a blend of: slowly degrading poly(D, L-lactide) (PLA), to reduce the production of acidic species during BSA release; and pore-forming poly(ethylene glycol) (PEG), to increase dif fusion of BSA and polymer degradation products out of the polymer. Methods. Microspheres were formulated from blends of PLA (Mw 145,000) and P EG (Mw 10,000 or 35,000) by using an anhydrous oil-in-oil emulsion and solv ent extraction (O/O) method. The polymer blend composition and phase miscib ility were examined by FT IR. and DSC, respectively. Microsphere surface mo rphology, water uptake, and BSA release kinetics were also investigated. Th e stability of BSA encapsulated in microspheres was examined by losses in p rotein solubility, SDS-PAGE, IEF, CD, and fluorescence spectroscopy. Results. PEG was successfully incorporated in PLA microspheres and shown to possess partial miscibility with PLA. A protein loading level of 5% (w/w) was attained in PLA/PEG microspheres with a mean diameter of approximately 100 mum. When PEG content was less than 20% in the blend, incomplete releas e of BSA was observed with the formation of insoluble, and primarily non-co valent aggregates. When 20%-30% PEG was incorporated in the blend formulati on, in vitro continuous protein release over 29 days was exhibited. Unrelea sed BSA in these formulations was water-soluble and structurally intact. Conclusions. Stabilization and controlled relaease of BSA from PLA/ PEG mic rospheres was achieved due to low acid and high water content in the blend formulation.