title: Glycyrrhetinic acid-graft-hyaluronic acid conjugate as a carrier for synergistic targeted delivery of antitumor drugs.
abstract: Glycyrrhetinic acid-graft-hyaluronic acid (HGA) conjugate was synthesized as a carrier for intravenous administration of paclitaxel (PTX), which combined hyaluronic acid (HA) and glycyrrhetinic acid (GA) as the active targeting ligands to liver tumor. In the present study, physicochemical characteristics, cellular uptake efficiency, and in vivo fates of HGA conjugates were investigated. HGA nanoparticles could readily load PTX with high efficiency up to 31.16 wt.% and entrapment efficiency to 92.02%. Moreover, PTX-loaded HGA nanoparticles exhibited more significant cytotoxicity to HepG2 cells than B16F10 cells due to simultaneously over-expressing HA and GA receptors. Meanwhile, the cellular uptake of nanoparticles was clearly enhanced in HepG2 and B16F10 cells compared to a normal fibroblast cell (HELF cells). In particular, more HGA nanoparticles were taken up by HepG2 cells than by B16F10 cells, which might be attributed to the affinity of multiple ligands of HA and GA to HepG2 cells. Furthermore, liver and tumor targeting activity of HGA nanoparticles was also confirmed by in vivo imaging analysis. The fluorescence signals of DiR-labeled HGA nanoparticles in tumor and liver were 2.88 and 1.83 folds stronger than that of the control, respectively. These results indicate HGA nanoparticles can be a potential drug carrier with "double target sites" for liver cancer therapy.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005260:Female; D006034:Glycyrrhetinic Acid / Q000737:chemistry* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D007275:Injections, Intravenous; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D006820:Hyaluronic Acid; D006034:Glycyrrhetinic Acid; D017239:Paclitaxel