文献类型：期刊文献

英文题名：The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-β-cyclodextrin inclusion complexes

作者：Ye, Ya-Jing[1];Wang, Yun[1];Lou, Kai-Yan[1];Chen, Yan-Zuo[1];Chen, Rongjun[2];Gao, Feng[1,3,4]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai 200237, Peoples R China;[2]Univ London Imperial Coll Sci Technol & Med, Dept Chem Engn, London SW7 2AZ, England;[3]E China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[4]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2015

卷号：10

起止页码：4309

外文期刊名：INTERNATIONAL JOURNAL OF NANOMEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000357577700001)】；

基金：The authors acknowledge financial support from the Fundamental Research Funds for the Central Universities (WY1213013 ECUST) and the Science and Technology Commission of Shanghai Municipality (STCSM, contract Nos 11DZ2260600 and 10DZ2220500). R Chen acknowledges financial support from the Imperial College of London.

语种：英文

外文关键词：dimethyl-beta-cyclodextrin; inclusion complex; chitosan nanoparticles; drug delivery; sustained release; paclitaxel

摘要：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)-beta-cyclodextrin (DM-beta-CD), using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-beta-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-beta-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-beta-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol (R)), the PTX/DM-beta-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC(0 -> 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-beta-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.