Targeted drug delivery to renal proximal tubule epithelial cells mediated by 2-glucosamine
Targeted drug delivery to renal proximal tubule epithelial cells mediated by 2-glucosamine
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DOI：
10.1016/j.jconrel.2013.02.001
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发表时间：
2013-04-28
影响因子：
10.8
通讯作者：
Sun, Xun
中科院分区：
文献类型：
--
作者：
Lin, Yan;Li, Yanping;Sun, Xun
为了开发新型肾脏靶向给药系统，我们以2-葡萄糖胺为配体合成了氨基甲酸泼尼松龙-葡萄糖胺缀合物（PCG），并考察了其潜在的靶向功效。体外研究表明，PCG能显著提高肾细胞对药物的摄取。巨蛋白受体抑制剂可显著降低PCG的特异性摄取。更重要的是，PCG在体内显示出良好的肾靶向性，静脉注射后60 min，偶联物在肾脏中的浓度是泼尼松龙组的8.1倍。PCG能明显逆转肾缺血再灌注（I/R）损伤动物模型的病情进展。此外，PCG对骨密度没有不良影响，而泼尼松龙导致严重的骨质疏松症。因此，它表明2-氨基葡萄糖可能是一个潜在的配体的肾脏靶向输送的泼尼松龙。(C)2013年爱思唯尔B。V.保留所有权利。
In order to develop a novel kidney-targeted drug delivery system, we synthesized prednisolone carbamate-glucosamine conjugate (PCG) using 2-glucosamine as a ligand, and investigated its potential targeting efficacy. In vitro studies demonstrated that PCG could remarkably improve the uptake of drug by kidney cells. And the specific uptake of PCG could be largely reduced by the inhibitors of megalin receptor. More importantly, PCG showed an excellent kidney targeting property in vivo, and the concentration of the conjugate in the kidney was 8.1-fold higher than that of prednisolone group at 60 min after intravenous injection. Besides, PCG could significantly reverse the disease progression in renal ischemia-reperfusion (I/R) injury animal models. Furthermore, PCG presented no adverse effect on bone density while prednisolone resulted in severe osteoporosis. Thus, it indicated that 2-glucosamine could be a potential ligand for kidney-targeted delivery of prednisolone. (C) 2013 Elsevier B. V. All rights reserved.