title: Glycyrrhizin surface-modified chitosan nanoparticles for hepatocyte-targeted delivery.
abstract: The aim of the present work was to investigate the potential utility of chitosan nanoparticles surface modified with glycyrrhizin (CS-NPs-GL) as new hepatocyte-targeted delivery vehicles. For this purpose, chitosan nanoparticles (CS-NPs) were prepared previously by ionic gelation process and glycyrrhizin was oxidized by sodium periodate to be conjugated to the surface of CS-NPs. The CS-NPs-GL obtained were first characterized for their morphology, particle size, zeta potential, association efficiency and in vitro release of adriamycin (ADR), using as a model drug. The nanoparticles were also labeled with rhodamine B isothiocyanate and their interaction with rat hepatocytes was examined by flow cytometry (FCM) and confocal laser microscopy (CLSM). The spherical nanoparticles prepared with oxidized GL/CS ratio of 0.14:1 (w/w) were in the 147.2nm size range, and exhibited a positive electrical charge (+9.3mV), and associated ADR quite efficiently (association efficiency: 91.7%) and showed lower extent of release (28% over 72h) in vitro. FCM and CLSM studies showed that CS-NPs-GL were preferentially accumulated in hepatocytes and the cellular uptake amount were 4.9 times more than that in hepatic nonparenchymal cells, and the uptake process was dependent on incubation time and dose of nanoparticles, which indicated that the internalization of these nanoparticles into hepatocytes was mostly mediated by a ligand-receptor interaction. In conclusion, CS-NPs-GL as a promising hepatocyte-targeted delivery carrier holds promise for further effective studies.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, People's Republic of China. Linah76@163.com
authors.forename: Aihua
authors.initials: A
authors.lastname: Lin
authors.forename: Yiming
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Jingbo
authors.initials: J
authors.lastname: Sun
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Wu
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Qineng
authors.initials: Q
authors.lastname: Ping
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D019695:Glycyrrhizic Acid / Q000737:chemistry*; D022781:Hepatocytes / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004337:Drug Carriers; D019695:Glycyrrhizic Acid; D004317:Doxorubicin; D048271:Chitosan