Thermosensitive core-rigid micelles of monomethoxy poly(ethylene glycol)-deoxy cholic acid

Background: Thermosensitive micelles with rigid cores that exhibit a reversible lower critical solution temperature at 30–35 °C can be applied for drug delivery. Method: Hydrophilic monomethoxy poly(ethylene glycol) was conjugated to hydrophobic deoxycholic acid to prepare monomethoxy poly(ethylene glycol)-deoxycholic acid (mPEG-DC). Micelle formation and thermosensitive solution behavior were studied using various methods, including hydrophobic dye solubilization, transmission electron microscopy, dynamic light scattering, turbidity measurement, microcalorimetry, and ¹H-NMR spectroscopy. Drug release from the thermosensitive micelles was demonstrated using estradiol, a model drug. Results: The mPEG-DC formed micelles with a critical micelle concentration of 0.05 wt.% and an average size of 15 nm. Aqueous mPEG-DC solutions exhibit a lower critical solution temperature (LCST) that is independent of concentration and reversible over heating and cooling cycles. The LCST transition is an entropically driven process involving dehydration of the PEG shell. The thermosensitive mPEG-DC micelles with rigid DC cores were applied as an estradiol delivery system in which estradiol was released, without initial burst, over the 16 days in a diffusion-controlled manner. Conclusions: This study suggests that mPEG-DCs form thermosensitive micelles with rigid cores that can function as an excellent diffusion-controlled hydrophobic drug delivery system without initial burst release. Graphical Abstract: Thermosensitive core-rigid micelles of monomethoxy poly(ethylene glycol)-deoxy cholic acid[Figure not available: see fulltext.]