title: Biodistribution characteristics of mannosylated and fucosylated O/W emulsions in mice.
abstract: Cell-specific drug delivery is one of the most promising strategies for improving therapeutic efficiency and minimizing systemic toxicity. Carrier systems devoted to receptor-mediated targeting need to be developed. In the case of liver-non-parenchymal cell-specific targeting systems, glycosylated emulsions have been developed as carriers for lipophilic drugs and/or peptides. This present study demonstrates the in vivo disposition behaviour and pharmacokinetic characteristics of mannosylated (Man-) and fucosylated (Fuc-) emulsions incorporated with cholesten-5-yloxy-N-(4-((1-imino-2-D-thiomannosylethyl)amino)alkyl)formamide (Man-C4-Chol) and its fucosylated derivatives (Fuc-C4-Chol), respectively. Man- (or Fuc-) emulsions are composed of soybean oil, EggPC and Man-C4-Chol (or Fuc-C4-Chol) in a weight ratio of 70:25:5. After intravenous administration to mice, these two types of [(3)H]cholesteryl hexadecyl ether (CHE)-labelled glycosylated emulsions were rapidly eliminated from the blood circulation and preferentially recovered in the liver. In contrast, bare (Bare-) emulsions composed of soybean oil:EggPC:cholesterol (Chol) in a weight ratio of 70:25:5 were more retained in the blood circulation. The hepatic uptake clearances of Man- and Fuc-emulsions were 3.3- and 4.0-times greater than that of Bare-emulsions. Interestingly, the hepatic uptake clearance of Fuc-emulsions was significantly higher that that of Man-emulsions. The uptake ratios by non-parenchymal cells (NPC) and parenchymal cells (PC) (NPC/PC ratio) for Bare-, Man- and Fuc-emulsions were found to be 0.4, 2.0 and 2.9, respectively. The hepatic uptakes of [(3)H]CHE-labelled Man- and Fuc-emulsions were reduced by pre-dosing with glycosylated proteins and liposomes. These results clearly support the conclusion that Man- and Fuc-emulsions are promising carrier systems for liver NPC-specific targeting via receptor-mediated mechanism.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Department of Drug Delivery Research, Japan.
authors.forename: Wassana
authors.initials: W
authors.lastname: Yeeprae
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics; D005643:Fucose / Q000737:chemistry / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008358:Mannose / Q000737:chemistry / Q000493:pharmacokinetics*; D051379:Mice; D010316:Particle Size; D013024:Soybean Oil / Q000737:chemistry; D013997:Time Factors; D014018:Tissue Distribution; D014867:Water / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D014867:Water; D005643:Fucose; D013024:Soybean Oil; D008358:Mannose