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.