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Amphiphilic Block Copolymers in Drug Delivery

We focus our efforts on developing drug delivery systems on the base of amphiphilic block copolymers. Several striking effects have been discovered using nonionic Pluronic block copolymers including hypersinsitization of multiple drug resistant cancers and drug transport across blood brain barrier. Pluronic-based formulation of anticancer drug, doxorubicin is currently in Phase I clinical trials.

A concept of "micellar microcontainer" was advanced in drug delivery, that is the use of block copolymer micelles as carriers for non-covalently incorporated drugs. Early work investigated blood brain transport of CNS drug in Pluronic micelles, which were targeted to the brain using specific antibodies (FEBS Lett 258:343-345, 1989). Effects of Pluronic unimers were further discovered in multidrug resistant (MDR) cancers resulting in cancer "hypersensitization" with respect to MDR drugs (Cancer Research 56:3626-3629, 1996). Recent studies illustrate how micelles affect cell trafficking by directing drugs towards vesicles. In contrast, unimers inhibit P-gp efflux system and release drug from vesicles in MDR type cells. These systems were used successfully in vivo to deliver drugs across intestinal and blood brain barriers, as well as to treat MDR and metastatic cancer tumors. As a result of these studies our views have evolved from "micellar microcontainer" to "libraries" of homologous block copolymers. With a set of copolymers differing in HLB, CMC and drug partitioning one adjusts a delivery system for best performance with a given drug and delivery situation. The copolymer "works" either as a microcontainer (micelle), or "biological response modifier" (unimer), or both.