Polymeric conjugates of drugs and antibodies for site-specific drug delivery

The synthesis of targetable conjugates of doxorubicin bound to N-(2-hydroxypropyl)methacrylamide copolymers was investigated. Anti-CD3 antibody against TCR/CD3 complex was used to target the conjugates to T-cells. The effect of structure of the oligopeptide spacer between the drug and polymer as well as of the polymer modification with the antibody on the rate of drug release from the polymeric carrier system incubated in vitro with cathepsin B or with a mixture of intracellular enzymes (tritosomes) is discussed. The results of in vitro drug-release experiments are correlated with the evaluation of T-cell cytotoxicity of targeted and nontargeted polymer-bound doxorubicin conjugates measured in vitro as the inhibition of Con-A stimulated growth of human peripheral blood lymphocytes (H-3-thymidine incorporation method).