Controlled release of polypeptides from polyanhydrides.

The effects of both polymer hydrophobicity and addition of stabilizers on the release and integrity of polymer-encapsulated proteins were studied. By using very hydrophobic poly[1,3-bis(p-carboxyhydroxy)hexane anhydride] with sucrose as an excipient, both recombinant bovine somatotropin and zinc insulin were released intact over 3 weeks. The released proteins appeared to maintain their integrity as judged by acidic reverse-phase HPLC, size-exclusion HPLC, radioimmunoassay, and conformation-sensitive immunoassays. Our results also suggest how polymer hydrophobicity can be used to enhance protein stability.