title: Hepatic-targeted gene delivery using cationic mannan vehicle.
abstract: The incidence of hepatic diseases continuously increases worldwide and causes significant mortality because of inefficient pharmacotherapy. Gene therapy is a new strategy in the treatment of hepatic diseases, but the disadvantages of insufficient retention in the liver and undesirable side effects hinder its application. In this study, we developed a novel nonviral vehicle targeted to liver. Mannan was cationized with spermine at varying grafted ratios to deliver the gene and was optimized in cytotoxicity and transfection in vitro. A spermine-mannan (SM)-based delivery system was proven to be hepatic targeted and was capable of prolonging the gene retention period in the liver. Moreover, SM at N/P of 20 was confirmed to be less interfered with by the serum. Optimized SM vehicle has relatively high hepatic transfection with almost no toxicity induction in the liver, which highlighted its potential in the treatment of hepatic diseases.
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, P. R. China.
authors.forename: Gui-Xin
authors.initials: GX
authors.lastname: Ruan
authors.forename: Tian-Yuan
authors.initials: TY
authors.lastname: Zhang
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Li
authors.forename: Xing-Guo
authors.initials: XG
authors.lastname: Zhang
authors.forename: You-Qing
authors.initials: YQ
authors.lastname: Shen
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000138:chemical synthesis* / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008351:Mannans / Q000737:chemistry*; D051379:Mice; D013096:Spermine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D002412:Cations; D008351:Mannans; D013096:Spermine
keywords: gene delivery; hepatic targeting; mannose receptor; spermine-mannan