Effect of mannose density on mannose receptor-mediated cellular uptake of mannosylated O/W emulsions by macrophages.
Effect of mannose density on mannose receptor-mediated cellular uptake of mannosylated O/W emulsions by macrophages.
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DOI：
10.1016/j.jconrel.2006.04.010
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发表时间：
2006-08
期刊：
影响因子：
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通讯作者：
Wassana Yeeprae;S. Kawakami;F. Yamashita;M. Hashida
中科院分区：
文献类型：
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作者：
Wassana Yeeprae;S. Kawakami;F. Yamashita;M. Hashida
糖接枝乳剂是亲脂性药物最有前途的细胞靶向系统之一。我们先前报道了由大豆油、EggPC和异戊烯-5-基氧基-N-（4-（（1-亚氨基-2-d-硫代甘露糖基乙基）氨基）烷基）甲酰胺（Man-C4-Chol）以70：25：5的比例组成的甘露糖基化（Man-）乳剂在小鼠静脉内给药后通过甘露糖受体介导的机制显著递送至肝非实质细胞（NPC）。由于通过受体介导机制的有效靶向在很大程度上受配体-受体相互作用控制，因此使用表达多种甘露糖受体的诱导巨噬细胞，研究了甘露糖密度对Man乳剂在小鼠体内分布和体外摄取方面的影响。静脉注射后，与含2.5% Man-C4-Chol的Man乳剂（Man-2.5-乳剂）和裸乳剂（裸乳剂）相比，含5.0%（Man-5.0-乳剂）和7.5%（Man-7.5-乳剂）Man-C4-Chol的Man乳剂从血液循环中迅速消除，并优先蓄积在肝脏-NPC中。体外研究表明，在甘露聚糖存在下，Man-5.0-和Man-7.5-乳剂的内化增加，摄取显著抑制。Man-C4-Chol含量的增加与共聚焦显微镜研究相对应。这些结果表明甘露糖乳剂的甘露糖密度通过甘露糖受体介导的机制在细胞识别和内化中起重要作用。
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.