Abstract
Recently, an attempt to target anticancer agents to the tumor cells by controlling their in vivo disposition behavior has attracted great interest in cancer chemotherapy. However, these approaches including monoclonal antibody conjugate can not achieve sufficiently effective targeting by the systemic administration due to ; (1) predominant uptake by the reticuloendothelial system such as the liver before arriving at the target site, (2) difficulty in escaping from the blood space to the interstices of the tumor, (3) lack of sufficient affinity to the tumor cell surface, (4) low efficiency in cellular internalization and drug release. In this paper, I will show our systematic approach to manage these problems in a design of immuno-conjugate of mitomycin C. Pharmacokinetic analysis of systemic disposition at a whole body level, local disposition in an organ perfusion system, and cellular association of the conjugates are discussed in relation to their physicochemical and biological characteristics. Based on these informations, we have designed macromolecular prodrugs of mitomycin C with therapeutic success. Possible application of drug delivery systems in a future cancer chemotherapy is also discussed.
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