Drug Release from Thermo-Responsive Self-assembled Polymeric Micelles Composed of Cholic Acid and Poly(N-isopropylacrylamide)

Cholic acid, conjugated with amine-terminated poly(W-isopropylacrylamide) (abbreviated as CA/ATPNIPAAm), was synthesized by a N, N'-dicyclohexyl carbodiimide (DCC)-mediated coupling reaction. Self-assembled CA/ATPNIPAAm micelles were prepared by a diafiltration method in aqueous media. The CA/ATPNIPAAm micelles exhibited a lower critical solution temperature (LCST) at $31.5^{\circ}C$. Micelle sizes measured by photon correlation spectroscopy (PCS) were approximately 31.6 $\times$$\times$ 5.8 nm. The CA/ATPNIPAAm micelles were spherical and their thermal size transition was observed by transmission electron microscope (TEM). A fluorescence probe technique was used for determining the micelle formation behavior of CA/ATPNIPAAm in aqueous solutions using Pyrene as a hydrophobic Probe. The critical micelle concentration (CMC) was evaluated as $8.9{\times}0^{-2}$ g/L. A drug release study was performed using indomethacin (IN) as a hydrophobic model drug. The release kinetics of IN from the CA/ATPNIPAAm micelles revealed a thermo-sensitivity by the unique character of poly(N-isopropylacrylamide) i.e. the release rate was higher at $25^{\circ}C$ than at $37^{\circ}C$.