title: Trans-resveratrol loaded chitosan nanoparticles modified with biotin and avidin to target hepatic carcinoma.
abstract: Conventional liver targeted system focuses on delivering drugs to liver, bringing toxicity on hepatic normal tissues. The purpose of this study is to construct a new system capable of specially targeting to hepatic carcinoma instead of the whole liver. Based on the fact that nanoparticles (NPs) bound with either biotin or avidin tend to accumulate in tumors and avidin-attached reagents were quickly eliminated from blood circulation and assembled in liver, trans-resveratrol loaded chitosan nanoparticles (CS-NPs), CS-NPs with the surface modified either by biotin (B-CS-NPs) or by both biotin and avidin (A-B-CS-NPs) were prepared and their physiochemical properties were investigated. The in vitro release profiles of the three NPs all conformed to bioexponential equation. Pharmacokinetic experiment indicated that A-B-CS-NPs rapidly assembled in liver after injection, with the highest liver targeting index of 2.70, while the modification of biotin attenuated the liver targeting ability of NPs. Inhibitory study on HepG2 cells declared that compared to trans-resveratrol solution and CS-NPs, both B-CS-NPs and A-B-CS-NPs significantly improved the anticancer activity. When incubated with HepG2 cells at high concentration for longer time, A-B-CS-NPs exhibited superior cytotoxicity than B-CS-NPs. This study exclaims that A-B-CS-NPs may be a potent drug delivery vector specially targeting to hepatic carcinoma.
authors.affiliation: Key Laboratory of Sichuan Province of Medicinal Chemistry, Chengdu University, Chengdu 610106, PR China.
authors.forename: Le
authors.initials: L
authors.lastname: Bu
authors.forename: Liang-Chun
authors.initials: LC
authors.lastname: Gan
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Guo
authors.forename: Feng-Zheng
authors.initials: FZ
authors.lastname: Chen
authors.forename: Qin
authors.initials: Q
authors.lastname: Song
authors.lastname: Qi-Zhao
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Gou
authors.forename: Shi-Xiang
authors.initials: SX
authors.lastname: Hou
authors.forename: Qian
authors.initials: Q
authors.lastname: Yao
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D001360:Avidin / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D001360:Avidin; D001710:Biotin; D048271:Chitosan; D000077185:Resveratrol