Thermosensitive nanosized micelles from cholesteryl-modified hydroxypropyl cellulose as a novel carrier of hydrophobic drugs

Abstract

The thermosensitive micelles based on the two series of cholesteryl-modified hydroxypropyl cellulose (series 1 and 2, respectively) were used as a promising drug carrier. The polymers 1a and 2a with side chain substitution degrees DChol = 0.7 and 2.1 mol% were selected for micelle preparation, respectively. Polymeric micelles were prepared by the co-solvent evaporation method. The aqueous self-assembly of the polymers was studied using fluorescence analysis and transmission electron microscopy (TEM). The critical micelle concentrations (CMCs) values of the various DChol of polymers were evaluated in the range of ca. 0.13–0.29 g/L which decreased with the increase of DChol in both series. Furthermore, the CMC values displayed a downtrend profile, with increasing the temperature. The polymer 1a with less DChol had lower CMC than that of polymer 2a. By using the naproxen as a hydrophobic model drug, the drug-loaded micelles were prepared. The TEM image of naproxen-loaded micelles of polymer 1a with 40 % drug-loading efficiency and 8 % loading capacity showed that micelles were regularly spherical in shape with a mean diameter of 70 nm. The unmodified HPC exhibited a lower critical solution temperature (LCST) of more than 41 °C in water, while polymeric micelles in aqueous solution presented an LCST of 38.7 °C. A drug release study was performed by dialysis method in phosphate-buffered solution at 25, 37 and 40 °C, respectively. The release kinetics of naproxen from the polymeric micelles revealed a thermosensitivity, since its release rate was higher at 40 °C than at 25 °C.