title: pH/redox responsive core cross-linked nanoparticles from thiolated carboxymethyl chitosan for in vitro release study of methotrexate.
abstract: A novel amphiphilic thiolated carboxymethyl chitosan was synthesized. It self-assembled into disulfide bond cross-linked nanoparticles in deionized water. The TEM showed that these nanoparticles had a core-shell structure with an average diameter of 160 nm. Dynamic light scattering showed that the nanoparticles were stable in water solution. The particle size changed with pH values and GSH concentrations, and reached a maximum diameter at pH 7.0 and 20mM GSH respectively, exhibiting an obvious pH/redox responsibility. Methotrexate was encapsulated in nanoparticles reaching encapsulation efficiency as much as 43.4%. Release profiles of methotrexate showed a release rate of 19 wt% in pH 7.4 buffer containing 10 μM GSH, whereas as high as 93 wt% in pH 5.0 buffer containing 20mM GSH, indicating that the nanoparticles may be used for tumor-specific drug release. The anticancer activity test in vitro showed that the inhibition rate of methotrexate-loaded nanoparticles against HeLa cells reached 90%.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China. Electronic address: 365464583@qq.com.
authors.forename: Xueqiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Guanghua
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China. Electronic address: yihuayin@aliyun.com.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Xiangqi
authors.initials: X
authors.lastname: Kong
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008727:Methotrexate / Q000008:administration & dosage* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D013438:Sulfhydryl Compounds; C514968:carboxymethyl-chitosan; D048271:Chitosan; D008727:Methotrexate
keywords: Carboxymethyl chitosan; Controlled drug release; Disulfide; Nanoparticle; Reduction responsibility; pH sensitivity