title: Mechanism of hepatic targeting via oral administration of DSPE-PEG-cholic acid-modified nanoliposomes.
abstract: In oral administration, gastrointestinal physiological environment, gastrointestinal epithelial cell membranes, and blood circulation are typical biological barriers to hepatic delivery of ligand-modified nanoparticle drug delivery systems. To elucidate the mechanism of oral hepatic targeting of cholic acid receptor-mediated nanoliposomes (LPs) (distearoyl phosphatidylethanolamine-polyethylene glycol-cholic acid-modified LPs, CA-LPs), evaluations were performed on colon cancer Caco-2 cell monolayers, liver cancer HepG2 cells, and a rat intestinal perfusion model. CA-LPs, ~100 nm in diameter, exhibited sustained-release behavior and had the greatest stability in rat gastrointestinal fluid and serum for both size and entrapment efficiency. CA-LPs demonstrated highest transport across Caco-2 cells and highest cellular uptake by HepG2 cells. The enhanced endocytosis of CA-LPs was found to be mediated by Na+/taurocholate cotransporting polypeptide and involved the caveolin-mediated endocytosis pathway. Further, we used fluorescence resonance energy transfer (FRET) technology to show that the CA-LPs maintained their structural integrity in part during the transport across the Caco-2 cell monolayer and uptake by HepG2 cells.
authors.affiliation: Department of Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D019826:Cholic Acid / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D004355:Drug Stability; D004705:Endocytosis / Q000187:drug effects; D031541:Fluorescence Resonance Energy Transfer; D056945:Hep G2 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D023421:Models, Animal; D053758:Nanoparticles / Q000737:chemistry*; D010477:Perfusion; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D013696:Temperature
chemical_list: D008081:Liposomes; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D019826:Cholic Acid
keywords: DSPE–PEG–cholic acid; FRET; hepatic targeting via oral administration; mechanism; nanoliposomes