Preparation, Characterization and in vitro Release of Chitosan-stavudine Conjugate Nano-prodrug  

作　　者：曾戎 WANG Zehu WANG Hongran CHEN Liqiang 乔仁忠 HU Liming LI Zelin 

机构地区：[1]Department of Materials Science and Engineering, College of Science and Engineering, Jinan University [2]State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, Beijing University of Chemical Technology [3]College of Life Science and Bioengineering, Beijing University of Technology

出　　处：《Journal of Wuhan University of Technology(Materials Science)》2013年第3期617-621,共5页武汉理工大学学报（材料科学英文版）

基　　金：Funded by the National Natural Science Foundation of China(Nos.20504018,20972014,20604010,20872010 and 20732004);the National Basic Research Program of China(No.2009CB930203)

摘　　要：Chitosan-stavudine （d4T） conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chitosan-5＇-O-succinyl-d4T conjugate was crosslinked with sodium tripolyphosphate （TPP） to obtain the chitosan-d4T conjugate nano-prodrug. The morphologies of chitosan-d4T conjugate nanoparticles were observed by transmission electron microscopy （TEM）, and their zeta potential, particle size, and polydispersity （size distribution） were measured by the dynamic light scattering （DLS） techniques. In vitro drug release studies at pH 1.1 and pH 7.4 indicate that the crosslinked chitosan-d4T conjugate nano-prodrug can prevent the coupled d4T from leaking out before entering the target viral reservoirs and provide a mild sustained release without the burst release. The results reveal that constructing conjugated chitosan nano-prodrugs may be a promising approach for improving the therapy efficacy of drugs in antiviral treatment.Chitosan-stavudine （d4T） conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chitosan-5＇-O-succinyl-d4T conjugate was crosslinked with sodium tripolyphosphate （TPP） to obtain the chitosan-d4T conjugate nano-prodrug. The morphologies of chitosan-d4T conjugate nanoparticles were observed by transmission electron microscopy （TEM）, and their zeta potential, particle size, and polydispersity （size distribution） were measured by the dynamic light scattering （DLS） techniques. In vitro drug release studies at pH 1.1 and pH 7.4 indicate that the crosslinked chitosan-d4T conjugate nano-prodrug can prevent the coupled d4T from leaking out before entering the target viral reservoirs and provide a mild sustained release without the burst release. The results reveal that constructing conjugated chitosan nano-prodrugs may be a promising approach for improving the therapy efficacy of drugs in antiviral treatment.

关 键 词：CHITOSAN STAVUDINE nano-prodrug polymeric conjugate 

分 类 号：TQ460.1[化学工程—制药化工]