title: In vitro and in vivo study of Gal-OS self-assembled nanoparticles for liver-targeting delivery of doxorubicin.
abstract: A liver-targeting drug delivery system for doxorubicin (DOX), that is, DOX-loaded self-assembled nanoparticles based on galactosylated O-carboxymethyl chitosan-graft-stearic acid conjugates (Gal-OS/DOX), has been prepared. The objective of the present study was to investigate the preparation, in vitro release, in vivo pharmacokinetics, and tissue distribution of Gal-OS/DOX nanoparticles. The drug-loaded nanoparticles were spherical in shape with mean size of 181.9 nm. In vitro release profiles indicated that the release of DOX from Gal-OS/DOX nanoparticles behaved with a sustained and pH-dependent drug release. Pharmacokinetics study revealed Gal-OS/DOX nanoparticles exhibited a higher AUC value and a prolonged residence time of drug in the blood circulation than those of DOX solution. Furthermore, Gal-OS/DOX nanoparticles increased the uptake of DOX in liver and spleen, but decreased uptake in heart, lung, and kidney in the tissue distribution study. These results suggested that the Gal-OS/DOX nanoparticles could prolong blood circulation time, enhance the liver accumulation, and reduce the side effect especially the cardiotoxicity of DOX. In conclusion, Gal-OS/DOX nanoparticles could be a promising drug delivery system for liver cancer therapy.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, People's Republic China.
authors.forename: Hejian
authors.initials: H
authors.lastname: Guo
authors.forename: Dianrui
authors.initials: D
authors.lastname: Zhang
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Caiyun
authors.initials: C
authors.lastname: Li
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.forename: Guangpu
authors.initials: G
authors.lastname: Liu
authors.forename: Leilei
authors.initials: L
authors.lastname: Hao
authors.forename: Jingyi
authors.initials: J
authors.lastname: Shen
authors.forename: Lisi
authors.initials: L
authors.lastname: Qi
authors.forename: Xinquan
authors.initials: X
authors.lastname: Liu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Luan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004339:Drug Compounding; D005690:Galactose / Q000737:chemistry*; D006031:Glycosylation; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013154:Spleen / Q000378:metabolism; D013228:Stearates / Q000737:chemistry*; D013229:Stearic Acids / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; C504164:O-carboxymethylchitosan; D013228:Stearates; D013229:Stearic Acids; C031183:stearic acid; D004317:Doxorubicin; D048271:Chitosan; D005690:Galactose
keywords: Drug delivery systems; Drug targeting; Nanoparticles; O-carboxymethyl chitosan; Pharmacodynamics; doxorubicin; liver targeting; pharmacokinetics; tissue distribution