Thermo-responsive polymer nanoparticles with a core-shell micelle structure as site-specific drug carriers

The success of most advanced drug delivery strategies requires development of sophisticated new site-specific carriers. Several new targeting methods use physical and chemical signals such as magnetic fields or changes in pH or temperature as targeting and triggering tools. In addition to site-specificity, the carrier should achieve passive targeting to evade the body's reticulo-endothelial system (RES) and exhibit long blood circulation times in order to efficiently distribute active drug to the site of action (active targeting). To fulfil these requirements, thermo-responsive polymeric micelles have been prepared from amphiphilic block copolymers composed of N-isopropylacrylamide (IPAAm) (a thermo-responsive outer shell) and styrene (St) (hydrophobic inner core). The polymeric micelle which is very stable in aqueous media was formed by the dialyzed method from DMF solution against water. The micelles 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 micelle concentration, providing a carrier that may have long blood circulation times and a low RES uptake. When the temperature is increased above the transition temperature of the thermo-responsive block chains (32 degrees C), the outer shell chains dehydrate and collapse, allowing aggregation between micelles and favoring binding interactions with cell membrane surfaces. Moreover, these changes are reversible. Hydrophobic molecules are shown to be incorporated into the inner hydrophobic core of the thermo-responsive micelles. Consequently, these micelles are Valuable for site-specific delivery of drugs using changes in temperature as a trigger. (C) 1997 Elsevier Science B.V.