Comparative study on sustained release of human growth hormone from semi-crystalline poly(L-lactic acid) and amorphous poly(D,L-lactic-co-glycolic acid) microspheres: morphological effect on protein release

Abstract

Recombinant human growth hormone (rhGH) was encapsulated by a double emulsion solvent evaporation method within two biodegradable microspheres having different polymer compositions. Semi-crystalline poly(L-lactic acid) (PLA) and amorphous poly(D,L-lactic-co-glycolic acid) (PLGA) were used for the encapsulation of hGH. Protein release profiles from the two rnicrospheres were comparatively evaluated with respect to their morphological difference. Both of the microspheres similarly exhibited rugged surface and porous internal structures, but their inner pore wall morphologies were quite different. The slowly degrading PLA microspheres had many nano-scale reticulated pores on the wall, while the relatively fast degrading PLGA microspheres had a non-porous and smooth wall structure. From the PLA microspheres, hGH was released out in a sustained manner with an initial similar to 20% burst, followed by constant release, and almost 100% complete release after a 1-month period. In contrast, the PLGA microspheres showed a similar burst level of similar to 20%, followed by much slower release, but incomplete release of similar to 50% after the same period. The different hGH release profiles between PLA and PLGA microspheres were attributed to different morphological characters of the pore wall structure. The inter-connected nano-porous structure of PLA microspheres was likely to be formed due to the preferable crystallization of PLA during the solvent evaporation process. (C) 2004 Elsevier B.V. All rights reserved.