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  • Title: Effect of mannose density on mannose receptor-mediated cellular uptake of mannosylated O/W emulsions by macrophages.
    Author: Yeeprae W, Kawakami S, Yamashita F, Hashida M.
    Journal: J Control Release; 2006 Aug 28; 114(2):193-201. PubMed ID: 16876282.
    Abstract:
    Carbohydrate grafted emulsions are one of the most promising cell-specific targeting systems for lipophilic drugs. We have previously reported that mannosylated (Man-) emulsions composed of soybean oil, EggPC and cholesten-5-yloxy-N-(4-((1-imino-2-d-thiomannosylethyl)amino)alkyl)formamide (Man-C4-Chol) with a ratio of 70:25:5 were significantly delivered to liver non-parenchymal cells (NPC) via mannose receptor-mediated mechanism after intravenous administration in mice. Since the efficient targeting through a receptor-mediated mechanism is largely controlled by ligand-receptor interaction, the effect of mannose density on Man-emulsions was studied with regard to both the disposition in vivo in mice and the uptake in vitro, using elicited macrophages which express a number of mannose receptors. After intravenous injection, Man-emulsions with 5.0% (Man-5.0-emulsions) and 7.5% (Man-7.5-emulsions) of Man-C4-Chol were rapidly eliminated from the blood circulation and preferentially accumulated in the liver-NPC compared with Man-emulsions with 2.5% of Man-C4-Chol (Man-2.5-emulsions) and bare emulsions (Bare-emulsions). The in vitro study showed increased internalization of Man-5.0- and Man-7.5-emulsions and significant inhibition of uptake in the presence of mannan. The enhanced uptake of Man-emulsions was related to the increasing of Man-C4-Chol content that corresponded to confocal microscopy study. These results suggest that the mannose density of Man-emulsions plays an important role in both cellular recognition and internalization via a mannose receptor-mediated mechanism.
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