Formulation and release characteristics of poly(lactic-co-glycolic acid) microspheres containing chemically modified protein

Chemical modification of proteins may influence their formulation into and release from polymeric microspheres. Three chemical modifications of rat serum albumin (RSA) were effected on the amine groups of this protein: conjugation with a polyanion using 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide, intermolecular cross‐linking using glutaraldehyde, and reductive alkylation using propyl aldehyde. The modified proteins had different physicochemical properties as well as improved encapsulation efficiencies compared with native RSA microspheres. The microspheres were incubated at 37°C for over one month to investigate the influence of protein modification on the release profiles. Microsphere degradation accelerated from the ninth day of the release studies and this coincided with an increase in the release rates. The degradation rates of poly(lactic‐co‐glycolic acid) microspheres containing either native or crosslinked RSA were more rapid than those containing either heparin conjugated or propylated RSA. This was in agreement with the release data, since the release of the native and crosslinked RSA were more rapid than those of the other modified proteins. The release profiles of the RSA‐heparin conjugates and the propylated RSA were approximately zero rather than first order between the tenth and thirtieth day of study. Chemical modification of protein may be a useful method to increase encapsulation efficiency and to decrease release rates of proteins that are to be used in microsphere formulations of potent therapeutic proteins.