POLYMERIC CONJUGATES OF DRUGS AND ANTIBODIES FOR SITE-SPECIFIC DRUG-DELIVERY

The synthesis of targetable conjugates of doxorubicin bound to N-(2-hy droxypropyl)methacrylamide copolymers was investigated. Anti-CD3 antib ody against TCR/CD3 complex was used to target the conjugates to T-cel ls. The effect of structure of the oligopeptide spacer between the dru g and polymer as well as of the polymer modification with the antibody on the rate of drug release from the polymeric carrier system incubat ed in vitro with cathepsin B or with a mixture of intracellular enzyme s (tritosomes) is discussed. The results of in vitro drug-release expe riments are correlated with the evaluation of T-cell cytotoxicity of t argeted and nontargeted polymer-bound doxorubicin conjugates measured in vitro as the inhibition of Con-A stimulated growth of human periphe ral blood lymphocytes (H-3-thymidine incorporation method).