title: The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-β-cyclodextrin inclusion complexes.
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 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-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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Ye
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Lou
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Yan-Zuo
authors.initials: YZ
authors.lastname: Chen
authors.affiliation: Department of Chemical Engineering, Imperial College London, London, United Kingdom.
authors.forename: Rongjun
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, People's Republic of China ; Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai, People's Republic of China ; Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D047392:beta-Cyclodextrins / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D047392:beta-Cyclodextrins; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D048271:Chitosan; D017239:Paclitaxel
keywords: chitosan nanoparticles; dimethyl-β-cyclodextrin; drug delivery; inclusion complex; paclitaxel; sustained release