The control of protein release from poly(DL-lactide co-glycolide) microparticles by variation of the external aqueous phase surfactant in the water-in oil-in water method

Poly(DL-lactide co-glycolide) microparticles below 5 mu m in size and containing ovalbumin (OVA), were prepared using the water-in oil-in water (w/o/w) technique with either polyvinyl alcohol (PVA) or polyvinylpyrrolidone (PVP) as stabilisers in the external aqueous phase. PVP-stabilised microparticles exhibited higher protein loading (8.2%, w/w relative to 4.0% for PVA stabilised microparticles) and increased core loading (encapsulation) of protein (70% vs. 30% for the PVA system). The use of PVP instead of PVA to prepare microparticles also resulted in reduction in the initial burst release of OVA, together with sustained protein release over 28 days and an increase in the protein delivery capacity from 35 to 45 mu g/mg particles. The changes in protein loading and delivery characteristics are considered to arise in part from an increase in the viscosity of the droplets of polymer solution, constituting the primary water-in oil emulsion, by diffusion of PVP from the external aqueous phase. Variation of the external aqueous phase surfactant provides a promising approach for improving the loading of therapeutic proteins and vaccine antigens within biodegradable microparticles and for modulating their release pattern. (C) 1998 Elsevier Science B.V.