title: Enhanced oral delivery of paclitaxel using acetylcysteine functionalized chitosan-vitamin E succinate nanomicelles based on a mucus bioadhesion and penetration mechanism.
abstract: In addition to being a physiological protective barrier, the gastrointestinal mucosal membrane is also a primary obstacle that hinders the oral absorption of many therapeutic compounds, especially drugs with a poor permeability. In order to resolve this impasse, we have designed multifunctional nanomicelles based on the acetylcysteine functionalized chitosan-vitamin E succinate copolymer (CS-VES-NAC, CVN), which exhibit marked bioadhesion, possess the ability to penetrate mucus, and enhance the oral absorption of a hydrophobic drug with a poor penetrative profile, paclitaxel. The intestinal absorption (Ka = 0.38 ± 0.04 min(-1), Papp = 0.059 cm · min(-1)) of CVN nanomicelles was greatly improved (4.5-fold) in comparison with paclitaxel solution, and CLSM (confocal laser scanning microscope) pictures also showed not only enhanced adhesion to the intestinal surface but improved accumulation within intestinal villi. The in vivo pharmacokinetics indicated that the AUC0-t (586.37 ng/mL · h) of CVN nanomicelles was markedly enhanced compared with PTX solution. In summary, the novel multifunctional CVN nanomicelles appear to be a promising nanocarrier for insoluble and poorly permeable drugs due to their high bioadhesion and permeation-enhancing capability.
authors.affiliation: Department of Biopharmaceutics and ‡Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang 110016, P. R. China.
authors.forename: He
authors.initials: H
authors.lastname: Lian
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.forename: Guolian
authors.initials: G
authors.lastname: Ren
authors.forename: Longfa
authors.initials: L
authors.lastname: Kou
authors.forename: Youxi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Han
authors.forename: Wenya
authors.initials: W
authors.lastname: Ding
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Ai
authors.forename: Chunnuan
authors.initials: C
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Sun
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry*; D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D008823:Micelles; D009093:Mucus; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013052:Spectrometry, X-Ray Emission; D013818:Thermogravimetry; D014810:Vitamin E / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D014810:Vitamin E; D048271:Chitosan; D017239:Paclitaxel; D000111:Acetylcysteine