Development of acid-sensitive copolymer micelles for drug delivery
E. R. Gillies and J. M. J. Fr�chet
Center for New Directions in Organic Synthesis, Department
of Chemistry, University of California, Berkeley, CA 94720, USA
Abstract: In recent years, supramolecular micellar assemblies
formed from amphiphilic block copolymers have been receiving attention
as potential drug carriers. The size of the carriers is ideal for avoiding
rapid renal exclusion and reticuloendothelial uptake, and enables
them to be targeted to certain tissues such as tumors. One important
issue determining the effectiveness of a micellar drug carrier is the
ability to control the time over which drug release takes place, or
to possibly trigger drug release at a specific location or time. The
mildly acidic pH encountered in tumor and inflammatory tissues as well
as in the endosomal and lysosomal compartments of cells has inspired
the development of micellar carriers capable of releasing their drug
load in response to small changes in pH. One approach to the development
of these systems has been to incorporate titratable groups
such as amines and carboxylic acids into the copolymer backbone, thus
altering the solubility of the polymer upon protonation and disrupting
micelle formation. Another approach has been to incorporate acid-degradable
linkages into the copolymer, either for direct attachment of the drug,
or to cause a structural change of such magnitude that micellar integrity
is lost and the drug is released.
*Lecture presented at the symposium "Controlling the
self assembly in macromolecular systems: From nature to chemistry to
functional properties", as part of the 39th IUPAC Congress and 86th
Conference of the Canadian Society for Chemistry: Chemistry at the Interfaces,
Ottawa, Canada, 10-15 August 2003. Other Congress presentations are
published in this issue, pp. 1295-1603.
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