使用聚乙烯吡咯烷酮作为聚合物载体来延长药物的血浆半衰期。

The use of PVP as a polymeric carrier to improve the plasma half-life of drugs.

作者信息

Kaneda Yoshihisa, Tsutsumi Yasuo, Yoshioka Yasuo, Kamada Haruhiko, Yamamoto Yoko, Kodaira Hiroshi, Tsunoda Shin-ichi, Okamoto Takayuki, Mukai Yohei, Shibata Hiroko, Nakagawa Shinsaku, Mayumi Tadanori

机构信息

Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.

出版信息

Biomaterials. 2004 Jul;25(16):3259-66. doi: 10.1016/j.biomaterials.2003.10.003.

DOI:10.1016/j.biomaterials.2003.10.003

PMID:14980420

Abstract

To achieve an optimum drug delivery such as targeting or controlled release utilizing bioconjugation with polymeric modifier, the conjugate between drugs and polymeric modifiers 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.

摘要

为了通过与聚合物修饰剂进行生物共轭实现诸如靶向或控释等最佳药物递送，药物与聚合物修饰剂之间的共轭物必须设计成在体内表现出理想的药代动力学特性。在本研究中，我们评估了各种非离子水溶性聚合物作为聚合物药物载体的生物药剂学性质。在静脉注射所有相同分子大小的非离子聚合物后，聚乙烯吡咯烷酮（PVP）显示出最长的平均驻留时间（MRT）。事实上，与聚乙烯乙二醇共轭的肿瘤坏死因子-α（PEG-TNF-α）相比，与PVP共轭的肿瘤坏死因子-α（PVP-TNF-α）在相同分子大小下循环时间更长。每种非离子聚合物修饰剂都表现出不同的组织分布。右旋糖酐在脾脏和肝脏中积累。聚二甲基丙烯酰胺（PDAAm）倾向于分布在肾脏中。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并使共轭药物在血液中定位的最合适的聚合物修饰剂。