l-Carnitine conjugated chitosan-stearic acid polymeric micelles for improving the oral bioavailability of paclitaxel

Drug Delivery

Qian Zhang¹  Hailan Mo¹  Wei Wu¹  Lanzhen Huang¹  Wei Zhang¹  Tan Yang¹  Jianfang Feng² 

[1] Department of Pharmacy, Guilin Medical University, Guilin, PR China;Department of Pharmacy, Guilin Medical University, Guilin, PR China;Department of Pharmacy, Guangxi University of Chinese Medicine, Nanning, PR Chin;

关键词: Micelle;    paclitaxel;    -carnitine;    oral bioavailability;    chitosan;   

DOI  :  10.1080/10717544.2020.1748762

来源: publisher

【 摘 要 】

A delivery system based on l-carnitine (LC) conjugated chitosan (CS)-stearic acid polymeric micelles has been developed for improving the oral bioavailability of paclitaxel (PTX) through targeting intestinal organic cation/carnitine transporter 2 (OCTN2). Stearic acid grafted chitosan (CS-SA), as micelle skeleton material, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The PTX-loaded micelles were prepared by solvent evaporation-hydration method, and the ligand LC was conjugated onto the micelle surface by anchoring its derivative stearoyl group to the lipophilic core of micelle. The modified polymeric micelles showed regular spherical shapes with small particle size of 157.1 ± 5.2 nm and high drug loading capacity of 15.96 ± 0.20 wt%, and the micelle stability in water was supported by low critical micelle concentration of 14.31 ± 0.21 μg/ml. The drug-loaded micelles presented a slow and incomplete in vitro release, and the pharmacokinetic studies indicated the micelle carriers increased the relative bioavailability of PTX to 165.8% against the commercial formulation. The enhancement effect on intestinal absorption was also confirmed by the intracellular uptake of Caco-2 cells. The proposed micelle carrier system manifested a prospective tool for oral drug delivery.

【 授权许可】

CC BY