Study on L-carnitine modified quercetin-coloading chitosan-stearic acid nanomicelles as oral paclitaxel delivery system: Preparation, characterization and in vivo intestine absorption in rats / 中草药

ABSTRACT

Objective: To prepare a drug delivery system based on L-carnitine modified and quercetin (QUE)-coloading chitosan-stearic acid (LC-SA/CS-SA) nanomicelles, investigate the properties of micelles, and evaluate the enhanced absorption effect of the micelles by in vivo intestinal absorption in rats. Methods: The CS-SA copolymer was synthesized by the amidation of free amino groups on CS. The chemical structure of CS-SA was characterized by Fourier transform-infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). Taking PTX was the main drug and quercetin as the auxiliary drug, the particle size distribution, Zeta potential, drug loading and entrapment efficiency of the micelles were investigated. The micromorphology of the micelles was observed by transmission electron microscope (TEM). The critical micelle concentration (CMC) of LC-SA/CS-SA micelles was measured by fluorescent probe method. The in vitro release of paclitaxel from polymeric micelles was evaluated by dialysis method. The absorption rate coefficient (Ka) of paclitaxel (PTX)-loaded micelles was assessed by in vivo intestine absorption in rats. Results: The results of FT-IR and 1HNMR indicated that the copolymer (CS-SA) was synthesized. The LC-SA/CS-SA@ QUE+PTX micelles showed regular spherical shapes with particle size of (148.3 ± 1.7) nm, PDI of 0.16 ± 0.07, Zeta potential of (24.600 ± 0.167) mV and CMC of 14.31 µg/mL. Compared to the commercial formulation of PTX, LC-SA/CS-SA@QUE+PTX micelles and LC-SA/CS-SA@PTX micelles showed significantly sustained release behaviors. The enhanced absorption effect of PTX in the micelle system was confirmed by intestine absorption test in rats. Conclusion: The LC-SA/CS-SA@QUE+PTX micelles, as a potential oral absorption promoter, enhanced the intestinal absorption of PTX in rats.