DEGRADATION OF POROUS POLY(ANHYDRIDE-CO-IMIDE) MICROSPHERES AND IMPLICATIONS FOR CONTROLLED MACROMOLECULE DELIVERY

The degradation properties of porous microspheres made using a new fam ily of polyanhydride copolymers, the poly(anhydride-co-imides), were s tudied. Poly[trimellitylimido-L-tyrosine-co-sebacic acid-co-1,3-bis(ca rboxyphenoxy)propane] microspheres, with and without entrapped bovine serum albumin (BSA) as a model protein, were made using the double emu lsion solvent evaporation process. Water penetration and anhydride bon d cleavage (polymer degradation) occurred rapidly (<5 days) compared t o the time scale of overall microsphere erosion (weeks to months) with most polymer compositions. Subsequent to bond cleavage, the ultimate erosion of the microsphere and release of entrapped BSA was due mainly to the slow dissolution of the individual hydrophobic monomers (TMA-T yr, SA and CPP) from the microsphere surface. BSA. was released at app roximately the same rate as the polymer eroded. Due to the fast degrad ation of anhydride bonds relative to microsphere erosion, initial poly mer molecular weight did not have a significant effect on macromolecul e release rates. Instead, monomer solubility correlated well with poly mer erosion and BSA release rates. This erosion mechanism leads to pre dictable drug release rates which may be appropriate for the delivery of many protein therapeutics, including vaccine antigens. The anhydrid e-imide copolymers were well tolerated in acute toxicity studies in ra ts and therefore show promise as biomaterials. (C) 1998 Elsevier Scien ce Ltd. All rights reserved.