Reduction of structural perturbations in bovine serum albumin by non-aqueous microencapsulation

Protein stability is a factor limiting the use of sustained-release devices in medical applications. The aim of this study was to reduce structural pe rturbations occurring in the frequently used model protein, bovine serum al bumin (BSA), upon microencapsulation in poly(D,L-lactide-co-glycolide) (PLG ) microspheres. Spray freeze-dried BSA was encapsulated into PLG microspheres by a complete ly nonaqueous oil-in-oil encapsulation procedure. FTIR spectroscopy was use d as a non-invasive method to quantify procedure-induced structural perturb ations in BSA. Spray-freeze drying of BSA caused significant structural per turbations that were minimized by co-spray freeze-drying BSA with trehalose . BSA-containing microspheres were produced by suspension of the powder by homogenization in methylene chloride containing PLG, followed by formation of coacervate droplets by the addition of silicon oil and hardening using t he solvent heptane. Resulting microspheres had dimensions of approximately 100 mum and the encapsulation efficiency for BSA was > 90%. FTIR data showe d that the structure of the BSA-trehalose formulation encapsulated into PLG microspheres was less perturbed than that of BSA obtained from buffer alon e. The results demonstrate that the structure-guided encapsulation approach in troduced for non-aqueous casting encapsulation procedures can be extended t o the non-aqueous production of pharmaceutically relevant PLG microspheres involving a complex encapsulation procedure.