The use of PVP as a polymeric carrier to improve the plasma half-life of drugs
The use of PVP as a polymeric carrier to improve the plasma half-life of drugs
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DOI：
10.1016/j.biomaterials.2003.10.003
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发表时间：
2004-07-01
期刊：
影响因子：
14
通讯作者：
Mayumi, T
中科院分区：
文献类型：
--
作者：
Kaneda, Y;Tsutsumi, Y;Mayumi, T
为了实现最佳的药物递送，例如利用与聚合物改性剂的生物缀合的靶向或控制释放，药物和聚合物改性剂之间的缀合物必须被设计为在体内显示出期望的药代动力学特征。在这项研究中，我们评估了各种非离子型水溶性聚合物作为聚合物药物载体的生物制药性能。聚乙烯吡咯烷酮（PVP）显示最长的平均停留时间（MRT）后，静脉注射的所有非离子聚合物具有相同的分子大小。事实上，肿瘤坏死因子-α（TNF-α）与PVP（PVP-TNF-α）生物缀合物的循环时间长于具有相同分子大小的TNF-α与聚乙二醇（PEG-TNF-α）生物缀合物。每种非离子聚合物改性剂显示出不同的组织分布。右旋糖酐在脾脏和肝脏中蓄积。聚二甲基丙烯酰胺（PDAAm）在肾脏中分布较集中。然而，PVP显示出最小的组织分布体积。这些结果表明PVP是延长药物循环寿命和使缀合药物在血液中定位的最合适的聚合物改性剂。(C)2003爱思唯尔有限公司。保留所有权利。
To achieve an optimum drug delivery such as targeting or controlled release utilizing bioconjugation with polymeric modifier, the conjugate between drugs and polymeric inodifiers must be designed to show desirable pharmacokinetic characteristics in vivo. In this study, we assessed the biopharmaceutical properties of various nonionic water-soluble polymers as polymeric drug carriers. Polyvinylpyrrolidone (PVP) showed the longest mean resident time (MRT) after i.v. injection of all nonionic polymers with the same molecular size. In fact, tumor necrosis factor-alpha (TNF-alpha) bioconjugated with PVP (PVP-TNF-alpha) circulated longer than TNF-alpha bioconjugated with polyethylene glycol (PEG-TNF-alpha) with the same molecular size. Each nonionic polymeric modifier showed a different tissue distribution. Dextran was accumulated in the spleen and liver. Polydimethylacrylamide (PDAAm) tended to distribute in the kidney. However, PVP showed the minimum volume of tissue distribution. These results suggested that PVP is the most suitable polymeric modifier for prolonging the circulation lifetime of a drug and localizing the conjugated drug in blood. (C) 2003 Elsevier Ltd. All rights reserved.