Poly(lactic acid) (PLA) and poly(lactic-co-GA) (PLGA) with low molecular weights were synthesized by a one-step polycondensation of lactic acid (LA) with glycolic acid (GA) molecules using stannous octoate as a catalyst at 160degreesC. A high yield (>80%) of all the polymers was obtained in the study. The PLA and PLGA copolymers were characterized by H-1-NMR, GPC, and DSC measurements, etc. We elaborated HSA-loaded microspheres based on PLA and PLGA copolymers with different monomer ratios (LA/GA = 85:15, 75:25, 65:35, and 50:50) by the solvent-extraction method based on the formation of double w/o/w emulsion. Microspheres were characterized in terms of the morphology, size, and encapsulation efficiency (E.E.). The highest E.E. (69.3%) of HSA was obtained for HSA-loaded PLGA (65/35) microspheres among all the formulations. In vitro matrix degradation and protein release of these microspheres were performed in phosphate-buffer saline (PBS; 154 mM, pH 7.4). The degradation profiles were characterized by measuring the loss of the microsphere mass and the decrease of the polymer intrinsic viscosity. The release profiles were investigated from the measurement of the protein presented in the release medium at various intervals. It was shown that the matrix degradation and protein-release profiles were highly LA/GA ratio-dependent. It is suggested that these matrix polymers may be optimized as carriers in protein- and peptide-delivery systems for different purposes. (C) 2003 Wiley Periodicals, Inc.