title: Preparation, characterization and in vitro release study of a glutathione-dependent polymeric prodrug Cis-3-(9H-purin-6-ylthio)-acrylic acid-graft-carboxymethyl chitosan.
abstract: In this work, an amphiphilic polymeric prodrug Cis-3-(9H-purin-6-ylthio)-acrylic acid-graft-carboxymethyl chitosan (PTA-g-CMCS) was designed and synthesized. In aqueous solution, this grafted polymer can self-assemble into spherical micelles with a size ranging from 104 to 285 nm and zeta potential ranging from -12.3 to -20.1 mV. For the release study, less than 24% of 6-Mercaptopurine (6-MP) was released from PTA-g-CMCS1 in the media containing 2 and 100 μM glutathione (GSH), whereas 37%, 54% and 75% of 6-MP was released from the media with GSH of 1, 2 and 10mM, respectively. Besides, pH and drug content of the polymeric prodrug only presented slight influence on the 6-MP release. MTT assay demonstrated that this system had higher inhibition ratio on HL-60 cells (human promyelocytic leukemia cells) in the presence of GSH and lower cytotoxicity on mouse fibroblast cell line (L929). Therefore, this nano-sized system is glutathione-dependent, and it can be employed as a potential carrier for the controlled release of 6-MP.
authors: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors: Xiao-Yu
authors: XY
authors: Gong
authors: Yi-Hua
authors: YH
authors: Yin
authors: Zhi-Jun
authors: ZJ
authors: Huang
authors: Bo
authors: B
authors: Lu
authors: Pei-Hu
authors: PH
authors: Xu
authors: Hua
authors: H
authors: Zheng
authors: Fu-Liang
authors: FL
authors: Xiong
authors: Hai-Xing
authors: HX
authors: Xu
authors: Xiong
authors: X
authors: Xiong
authors: Xing-Bao
authors: XB
authors: Gu
mesh_terms: D000179:Acrylates / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D015122:Mercaptopurine / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis; D011687:Purines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000179:Acrylates; D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D011687:Purines; C514968:carboxymethyl-chitosan; C577207:cis-3-(9H-purin-6-ylthio)-acrylic acid; C577208:cis-3-(9H-purin-6-ylthio)-acrylic acid-g-carboxymethyl chitosan; D048271:Chitosan; D015122:Mercaptopurine; D005978:Glutathione