Stabilization of proteins encapsulated in injectable poly (lactide-co-glycolide)

Controlled release from biodegradable polymers is a novel approach to repla ce daily painful injections of protein drugs. A major obstacle to developme nt of these polymers is the need to retain the structure and biological act ivity of encapsulated proteins during months of incubation under physiologi cal conditions. We encapsulated bovine serum albumin (BSA) in injectable po ly(DL-lactide-co-glycolide) (PLGA) 50/50 cylindrical implants and determine d the mechanism of BSA instability. Simulations of the polymer microclimate revealed that moisture and acidic pH (<3) triggered unfolding of encapsula ted BSA, resulting in peptide bond hydrolysis and noncovalent aggregation. To neutralize the acids liberated by the biodegradable lactic/glycolic acid -based polyester we coincorporated into the polymer an antacid, Mg(OH)(2), which increased microclimate pH and prevented BSA structural losses and agg regation for over one month. We successfully applied this stabilization app roach in both cylinder- and microsphere-injectable configurations and for d elivery of angiogenic basic fibroblast growth factor and bone-regenerating bone morphogenetic protein-2.