PROTEIN RELEASE FROM POLY(EPSILON-CAPROLACTONE) MICROSPHERES PREPAREDBY MELT ENCAPSULATION AND SOLVENT EVAPORATION TECHNIQUES - A COMPARATIVE-STUDY

Poly(epsilon-caprolactone) (PCL) microspheres containing c. 3% bovine serum albumin (BSA) were prepared by melt encapsulation and solvent ev aporation techniques. PCL, because of its low T-m, enabled the melt en capsulation of BSA at 75 degrees C thereby avoiding potentially toxic organic solvents such as dichloromethane (DCM). Unlike the solvent eva poration method, melt encapsulation led to 100% incorporation efficien cy which is a key factor in the microencapsulation of water-soluble dr ugs. Examination of the stability of the encapsulated protein by sodiu m dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) demon strated that protein integrity was unaffected by both methods of encap sulation. In vitro release of the protein into phosphate buffer examin ed at 37 degrees C from microspheres prepared by both techniques showe d that the release rate from melt-encapsulated microspheres was somewh at slower compared to the release from solvent-evaporated spheres. Bot h released around 20% of the incorporated protein in 2 weeks amounting to approximately 6.5 mu g mg(-1) of microspheres. Although the diffus ivity of macromolecules in PCL is rather low, it is shown that PCL mic rospheres are capable of delivering sufficient quantity of proteins by diffusion for prolonged periods to function as a carrier for many vac cines. Unlike poly(lactic acid) (PLA) and poly(glycolic acid) (PGA) po lymers which generate extreme acid environments during their degradati on, the delayed degradation characteristics of PCL do not generate an acid environment during protein release and, therefore, may be advanta geous for sustained delivery of proteins and polypeptides.