Drug release from thermo-responsive self-assembled polymeric micelles composed of cholic acid and poly(N-isopropylacrylamide)

Cholic acid, conjugated with amine-terminated poly(N-isopropylacrylamide) ( abbreviated as CA/ATPNIPAAm), was synthesized by a N, N'-dicyclohexyl carbo diimide (DCC)-mediated coupling reaction. Self-assembled CA/ATPNIPAAm micel les were prepared by a diafiltration method in aqueous media. The CA/ATPNIP AAm micelles exhibited a lower critical solution temperature (LCST) at 31.5 degrees C. Micelle sizes measured by photon correlation spectroscopy (PCS) were approximately 31.6 +/- 5.8 nm. The CA/ATPNIPAAm micelles were spheric al and their thermal size transition was observed by transmission electron microscope (TEM). A fluorescence probe technique was used for determining t he micelle formation behavior of CA/ATPNIPAAm in aqueous solutions using py rene as a hydrophobic probe. The critical micelle concentration (CMC) was e valuated as 8.9 x 10(-2) g/L. A drug release study was performed using indo methacin (IN) as a hydrophobic model drug. The release kinetics of IN from the CAI ATPNIPAAm micelles revealed a thermo-sensitivity by the unique char acter of poly(N-isopropylacrylamide) i.e. the release rate was higher at 25 degrees C than at 37 degrees C.