Biodistribution characteristics of mannosylated and fucosylated O/W emulsions in mice

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-nthiomannosylethyl)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 [H-3]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 [H-3]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.