THERMORESPONSIVE POLYMER NANOPARTICLES WITH A CORE-SHELL MICELLE STRUCTURE AS SITE-SPECIFIC DRUG CARRIERS

The success of most advanced drug delivery strategies requires develop ment of sophisticated new site-specific carriers. Several new targetin g methods use physical and chemical signals such as magnetic fields or changes in pH or temperature as targeting and triggering tools. In ad dition to site-specificity, the carrier should achieve passive targeti ng to evade the body's reticulo-endothelial system (RES) and exhibit l ong blood circulation times in order to efficiently distribute active drug to the site of action (active targeting). To fulfil these require ments, thermo-responsive polymeric micelles have been prepared from am phiphilic block copolymers composed of N-isopropylacrylamide (IPAAm) ( a thermo-responsive outer shell) and styrene (St) (hydrophobic inner c ore). The polymeric micelle which is very stable in aqueous media was formed by the dialyzed method from DMF solution against water. The mic elles have a unimodal size distribution (24+/-4 nm) and CMC was around 10 mg/l. These micelles have a small diameter with a low critical mic elle concentration, providing a carrier that may have long blood circu lation times and a low RES uptake. When the temperature is increased a bove the transition temperature of the thermo-responsive block chains (32 degrees C), the outer shell chains dehydrate and collapse, allowin g aggregation between micelles and favoring binding interactions with cell membrane surfaces. Moreover, these changes are reversible. Hydrop hobic molecules are shown to be incorporated into the inner hydrophobi c core of the thermo-responsive micelles. Consequently, these micelles are Valuable for site-specific delivery of drugs using changes in tem perature as a trigger. (C) 1997 Elsevier Science B.V.