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已发表论文

装载紫杉醇 (Paclitaxel)/二甲基-β-环糊精包合物的壳聚糖纳米颗粒的制备、表征和药物动力学研究

 

Authors Ye YJ, Wang Y, Lou KY, Chen YZ, Chen R, Gao F

Published Date July 2015 Volume 2015:10 Pages 4309—4319

DOI http://dx.doi.org/10.2147/IJN.S83508

Received 25 February 2015, Accepted 20 April 2015, Published 3 July 2015

Approved for publication by Dr Lei Yang

Abstract: A novel biocompatible and biodegradable drug-delivery nanoparticle (NP) has been developed to minimize the severe side effects of the poorly water-soluble anticancer drug paclitaxel (PTX) for clinical use. PTX was loaded into the hydrophobic cavity of a hydrophilic cyclodextrin derivative, heptakis (2,6-di-O -methyl)-β-cyclodextrin (DM-β-CD), using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-β-CD inclusion complex dramatically enhanced the solubility of PTX in water and was directly incorporated into chitosan (CS) to form NPs (with a size of 323.9–407.8 nm in diameter) using an ionic gelation method. The formed NPs had a zeta potential of +15.9–23.3 mV and showed high colloidal stability. With the same weight ratio of PTX to CS of 0.7, the loading efficiency of the PTX/DM-β-CD inclusion complex-loaded CS NPs was 30.3-fold higher than that of the PTX-loaded CS NPs. Moreover, it is notable that PTX was released from the DM-β-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol®), the PTX/DM-β-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC0→24h (the area under the plasma drug concentration–time curve over the period of 24 hours) and mean residence time by 2.7-fold and 1.4-fold, respectively. Therefore, the novel drug/DM-β-CD inclusion complex-loaded CS NPs have promising applications for the significantly improved delivery and controlled release of the poorly water-soluble drug PTX or its derivatives, thus possibly leading to enhanced therapeutic efficacy and less severe side effects.
Keywords: dimethyl-β-cyclodextrin, inclusion complex, chitosan nanoparticles, drug delivery, sustained release, paclitaxel






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