Functional and site-specific macromolecular micelles as high potential drug carriers

Since several years, macromolecular micelles based on amphiphilic block copolymers have attracted much interest as drug carriers. These micelles show a long term blood circulation time resulting from their small diameter and the steric repulsion created by the poly(ethylene oxide) chains which constitute micelle corona, as well as from their high thermodynamic stability. Besides this long term blood circulation time generating a passive targeting, an active targeting, chemical or physical affinity targeting, might allow the preparation of more efficient drug carriers. In order to obtain such double targeting properties, we have prepared two kinds of macromolecular micelles. The first one is based on amphiphilic poly(ethylene oxide)/poly(beta-benzyl L-aspartate) -PEO/PBLA- block copolymers having hydroxy groups at the free end of PEO chains. As a result of their structure, such micelles have hydroxy groups on their outer-shell which can be further modified in order to introduce a targeting moiety (sugar, etc.). The characteristics (diameter, critical micellar concentration (cmc), drug loading capacity) have been determined. Moreover, doxorubicin loaded alpha-hydroxy PEO/PBLA micelles have been shown to be slightly more cytotoxic than the corresponding alpha-methoxy PEO/PBLA micelles. The second type of micelles is based on thermosensitive amphiphilic poly(N-isopropyl acrylamide)/polystyrene -PIPAAm/PSt- block copolymers. Such micelles have a small diameter and a low cme in addition to thermosensitivity properties which are similar to those of PIPAAm. (C) 1999 Elsevier Science B.V. All rights reserved.