Development of biodegradable nanoparticles for liver-specific ribavirin delivery. J
Development of biodegradable nanoparticles for liver-specific ribavirin delivery. J
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开发用于肝脏特异性利巴韦林递送的可生物降解纳米颗粒。
DOI：
10.1002/jps.24219
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
T
中科院分区：
文献类型：
--
作者：
Ishihara;T.;Kaneko;K.;Ishihara;T. and Mizushima;T
利巴韦林是一种用于治疗慢性丙型肝炎的抗病毒药物。然而，利巴韦林会引起严重的副作用，例如溶血性贫血。在本研究中，我们制备了可生物降解的纳米颗粒作为利巴韦林载体来调节药物的药代动力学。在铁 (III) 存在下，采用溶剂扩散法，由聚（d,l-乳酸）均聚物和阿拉伯半乳聚糖（AG）-聚（l-赖氨酸）缀合物的共混物制备了包封利巴韦林单磷酸（RMP）的纳米颗粒。 RMP 有效且稳定地嵌入纳米颗粒中，并在 37°C 的磷酸盐缓冲盐水中逐渐释放 37 天。通过测量 zeta 电位并使用半乳糖结合凝集素进行纳米颗粒的聚集测试来验证纳米颗粒表面的 AG 涂层。此外，纳米颗粒在培养的 HepG2 细胞中被有效内化。静脉注射负载 RMP 的纳米颗粒后，利巴韦林急剧积累到小鼠的肝脏中，此后利巴韦林含量在至少 7 天内逐渐下降。我们的结果表明成功开发了具有双重功能的纳米颗粒，靶向肝脏并持续释放利巴韦林，并表明目前的策略有助于推进利巴韦林作为慢性丙型肝炎治疗剂的临床应用。 © 2014 Wiley periodicals, Inc. 和美国药剂师协会。
Ribavirin is an antiviral drug used for the treatment of chronic hepatitis C. However, ribavirin induces severe side effects such as hemolytic anemia. In this study, we prepared biodegradable nanoparticles as ribavirin carriers to modulate the pharmacokinetics of the drug. The nanoparticles encapsulating ribavirin monophosphate (RMP) were prepared from the blend of poly(d,l-lactic acid) homopolymer and arabinogalactan (AG)–poly(l-lysine) conjugate by using the solvent diffusion method in the presence of iron (III). RMP was efficiently and stably embedded in the nanoparticles and gradually released for 37 days in phosphate-buffered saline at 37°C. The coating of AG on the nanoparticles surfaces was verified by measuring the zeta potentials and performing an aggregation test of the nanoparticles using galactose-binding lectin. Moreover, the nanoparticles were efficiently internalized in cultured HepG2 cells. Ribavirin was drastically accumulated to the liver of mice after intravenous administration of the RMP-loaded nanoparticles, after which the ribavirin content gradually decreased for at least 7 days. Our results indicated successful development of nanoparticles with dual functions, targeting to the liver and sustained release of ribavirin, and suggested that the present strategy could help to advance the clinical application of ribavirin as a therapeutic agent for chronic hepatitis C. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.