Biological Effects and Antitumor Activity Induced by Benzocaine Conjugated Anionic Polymers

Abstract

Three maleic anhydride copolymers [poly(maleic anhydride-vinyl acetate), poly(maleic anhydride-styrene) and poly(maleic anhydride-methyl methacrylate)] were prepared as well as the corresponding benzocaine conjugates. The maleic anhydride moiety was hydrolyzed to the corresponding polycarboxylate anions and then biologically evaluated using pyran copolymer as the standard. All of the polymers showed internal organ toxicity of the liver, kidneys and spleen which increased with increasing molecular weight, however, the benzocaine derivatives decreased this effect in most cases. The biological evaluations included hemoglobin levels, hematocrit levels, red blood indices and mean cell volumes which were increased on an average of 50%. The blood protein profiles were not changes significantly; on average they were changed about ±50%. The unmodified copolymers decreased the major serum and cholesterol levels by ∼75%. The copolymers (with or without) benzocaine decreased both the blood sugar and enzyme profiles. The antitumour activity was evaluated against Walker carcinosarconoma; although the benzocaine enhanced these effects, only pyran and the 18,000 Mw benzocaine-modified poly(maleic anhydride-vinyl acetate) produced significant effects.