Release of bovine serum albumin from preformed porous microspheres of poly(L-lactic acid)

Preformed porous microspheres of poly(L-lactic acid) (Accurel(R)) have been shown to sustain the release of highly water soluble solutes, like dextran and mannitol, for a time period of more than 4 months. The purpose of this investigation was to mechanistically characterize the release of a model p rotein, bovine serum albumin (BSA), from these highly porous microspheres. The microspheres were loaded with [C-14]BSA in three different concentratio ns of 0.06, 0.26 and 0.59% w/w. The rate of release of [C-14]BSA from micro spheres was correlated to media ([H-3]PBS) uptake. The release of BSA showe d a biphasic pattern; an initial rapid release, followed by a sustained rel ease. The initial burst of BSA was found to be inversely proportional to BS A loading and highly correlated to water penetration. The sustained release phase was independent of water penetration kinetics. Washing the microsphe res did not remove either the surface bound BSA or the BSA incorporated in the microsphere matrix, indicating the tight binding of BSA to highly porou s microspheres. Furthermore, addition of a surfactant induced a dramatic in crease in the amount of BSA released, suggesting that the release is contro lled by the surface binding of BSA to the polymer. Also, the release rate o f BSA beyond the initial burst was found to be much slower than for the low er MW macromolecules like dextran at a similar level. The data from the pre sent work suggests the BSA-polymer interaction to be a major contributing f actor in explaining the overall BSA release kinetics.