Preparation of non-porous microspheres with high entrapment efficiency of proteins by a (water-in-oil)-in-oil emulsion technique

Emulsification-solvent removal methods have been widely used for encapsulat ing bioactive macromolecules like proteins and polypeptides in biodegradabl e polymers. We report, a (water-in-oil)-in-oil emulsion technique wherein p roteins and polypeptides differing in molecular weight and shape were encap sulated in polymers of current biomedical interest. When an oil was used as the processing medium in combination with a carefully selected mixed solve nt system such that a stable (w/o(1)/o(2) emulsion is formed and solvents a re removed by a combination of extraction and evaporation, the entrapment e fficiency was high and the product nonporous. The entrapment efficiency of globular proteins exceeded 90% while that of fibrous proteins was around 70 %. Fracture studies revealed that the polymer matrix was dense. The mechani sm of entrapment involved solvent-induced precipitation of the protein as t he microspheres were being formed. The principle of the method will find us e in preparation of non-porous polymer microparticles with reduced burst ef fect. (C) 1999 Elsevier Science B.V. All rights reserved.