Design, synthesis, and pr eliminary characterization of tyrosine-containing polyarylates: New biomaterials for medical applications

Five structurally related, aliphatic polyarylates were synthesized from tyrosine-derived diphenols and diacids. The diphenols were a homologous series of three desaminotyrosyl-tyrosine alkyl esters (ethyl, hexyl, octyl) which had previously been used in the synthesis of mechanically strong and tissue-compatible polycarbonates. The diacids (succinic acid, adipic acid, sebacic acid) were selected among compounds that were known to be of low systemic toxicity. By using different diacids as comonomers, the flexibility of the polymer backbone could be varied while the desaminotyrosyl-tyrosine alkyl esters provided pendent chains of various length. Some of the thermal and mechanical properties of the five polymers could be correlated to their chemical structure: the glass transition temperature decreased from 53 to 13°C, and the tensile modulus (measured at room temperature) decreased from 1500 to about 3 MPa when the length of the aliphatic diacid in the polymer backbone and/or the length of the alkyl ester pendent chain was increased. The presence of an arylate bond in the polymer backbone introduced a hydrolytically labile linkage into the polymer structure. Under physiological conditions in vitro all polymers degraded: thin films retained only about 30-40% of their initial molecular weight (M_w) after 26 weeks of storage in phosphate buffer solutions (pH 7.4) at 37°C. Release studies with p-nitroaniline as a model drug indicated that a diffusion controlled release process occurred. The rate of p-nitroaniline release could be correlated with the glass transition temperature of the polymer.