In vitro protein release and degradation of poly-dl-lactide-poly(ethylene glycol) microspheres with entrapped human serum albumin: Quantitative evaluation of the factors involved in protein release phases

Purpose. To quantitatively evaluate the correlations between the amount of initial burst release and the surface-associated protein, and between the o nset time for the second burst release and the matrix polymer degradation. Methods. Human serum albumin (HSA) was microencapsulated in polylactide (PL A) and poly-dl-lactide-poly(ethylene glycol) (PELA) with PEG contents of 5, 10, 20, and 30%, respectively, using the solvent extraction procedure base d on formation of double emulsion w/o/w. Microspheres with similar particle size (1.7-2.0 mum), similar protein entrapment (2.1-2.8%) but different su rface-associated proteins (9.3-53.6%) were used to evaluate the in vitro ma trix degradation and protein release profiles. Degradation was characterize d by studying the intrinsic viscosity decrease, medium pH change, and weigh t loss of the microspheres. Results. The matrix degradation and protein release profiles were highly de pendent on the polymer composition of the microspheres. Faster decreases in the intrinsic viscosity of recovered matrix polymer, the microspheres weig ht, and the pH of degradation medium, and earlier onsets for the break in i ntrinsic viscosity reduction and the mass loss were detected for PELA micro spheres with higher PEG content. The hydration and swelling of microspheres matrix contributed greatly to the degradation of matrix polymer. The HSA r elease showed triphasic profile and involved two mechanisms for all the mic rosphere samples. Smaller amount of initial burst release, larger gradual r elease rate, and earlier onset for the second burst release were observed f or HSA from matrix polymer with higher PEG content. The extent of the initi al burst release was quantitatively related with the surface-associated pro tein. The second burst release of HSA was observed to occur within 1 week a fter the onset for mass loss, which was also the break in the intrinsic vis cosity reduction rate. Conclusion. Protein release profiles could be rationalized by optimizing th e matrix polymer degradation and microsphere characteristics.