NEW BIODEGRADABLE POLYMERS OF L-LACTIC ACID AND AROMATIC HYDROXY-ACIDS AND THEIR APPLICATIONS IN DRUG DELIVERY SYSTEMS

New biodegradable polymers with an aromatic ring in the main chain and with aromatic rings in both the main chain and the pendant group were synthesized by the direct polycondensation of L-lactic acid (LA) and aromatic hydroxy acids such as DL-mandelic (MA), p-hydroxybenzoic (HBA), p-hydroxyphenylacetic (HPAA), and p-hydroxyphenylpropionic (HPPA) acids, using polymer systems composed of LA/HBA, LA/HPAA, LA/HPPA, and LA/MA/HPPA, for example. In an LA copolymer, the degree of degradation in vivo markedly decreases with increasing proportion of aromatic hydroxy acid in the system, in which the degradation behavior resulted in either a linear or a parabolic profile according to the kind of copolymer and its composition. In contrast, an S-type degradation pattern was obtained in a ternary polymer system (e.g. poly(LA/MA/HPPA), 80:10:10 mol%). Estramustine was incorporated into the ternary polymer formulation in the form of small cylinders followed by subcutaneous implantation into male rats. The pharmacological effect of drug released in vivo from the formulation was examined by measuring the changes in weight of the accessory sex organs of male rats, the results demonstrating the maintenance of efficacious pharmacological action over a period of approx. 10 weeks.