The targeting of anionized polyvinylpyrrolidone to the renal system
The targeting of anionized polyvinylpyrrolidone to the renal system
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DOI：
10.1016/j.biomaterials.2003.10.097
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发表时间：
2004-08-01
期刊：
影响因子：
14
通讯作者：
Mayumi, T
中科院分区：
文献类型：
--
作者：
Kodaira, H;Tsutsumi, Y;Mayumi, T
我们报道了由乙烯吡咯烷酮和马来酸组成的共聚物在静脉注射后选择性地分布到肾脏。为了进一步优化肾脏给药系统，我们评估了阴离子化聚乙烯吡咯烷酮（PVP）衍生物在小鼠静脉给药后的肾脏靶向能力。阴离子化PVP衍生物从血液中的消除随着阴离子基团的增加而减少，并且羧化PVP和磺化PVP从血液中的清除率几乎相似。但羧化PVP在肾脏中有效蓄积，而磺化PVP则迅速随尿排出。肾脏中羧化PVP的水平约为磺化PVP的5倍。此外，静脉注射后，羧基化PVP在体内被肾近端肾小管上皮细胞有效摄取。这些阴离子化PVP衍生物在体外对肾小管细胞和内皮细胞没有显示出任何细胞毒性。因此，这些羧化和磺化的PVP可以分别是用于药物递送至肾脏和膀胱的有用的聚合物载体。(C)2003 Elsevier Ltd.保留所有权利。
We reported that the co-polymer composed of vinylpyrrolidone and maleic acid selectively distributed into the kidneys after i.v. injection. To further optimize the renal drug delivery system, we assessed the renal targeting capability of anionized polyvinylpyrrolidone (PVP) derivatives after intravenous administration in mice. The elimination of anionized PVP derivatives from the blood decreased with increasing anionic groups, and the clearance of carboxylated PVP and sulfonated PVP from the blood was almost similar. But carboxylated PVP efficiently accumulated in the kidney, whereas sulfonated PVP was rapidly excreted in the urine. The renal levels of carboxylated PVP were about five-fold higher than sulfonated PVP. Additionally, carboxylated PVP was effectively taken up by the renal proximal tubular epithelial cells in vivo after i.v. injection. These anionized PVP derivatives did not show any; cytotoxicity against renal tubular cells and endothelial cells in vitro. Thus, these carboxylated and sulfonated PVPs may be useful polymeric carriers for drug delivery to the kidney and bladder, respectively. (C) 2003 Elsevier Ltd. All rights reserved.