Development of liver-specific ribavirin-loaded nanoparticles with reduced cytotoxicity
Development of liver-specific ribavirin-loaded nanoparticles with reduced cytotoxicity
复制标题
开发具有降低细胞毒性的肝脏特异性利巴韦林纳米颗粒
DOI：
10.1080/2331205x.2017.1418133
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Ishihara T.
中科院分区：
文献类型：
--
作者：
Kaneko K;Ishihara T.
利巴韦林被广泛用于多种类型的联合化疗，用于治疗慢性丙型肝炎。为了将利巴韦林输送到肝脏并减少其副作用，我们先前制备了单磷酸利巴韦林纳米粒，由聚(D，L-乳酸)、阿拉伯半乳糖-聚(L-赖氨酸)结合物和铁离子组成。在本研究中，纳米粒是在没有聚L-赖氨酸的情况下开发的，以避免细胞毒性。以端氨基(S)为端基的聚(D，L-乳酸)与阿拉伯半乳糖-聚(L-谷氨酸)偶联物的混合物成功地制备了纳米粒。RMP稳定地负载在纳米粒中，并在生理条件下逐渐释放。此外，在体外和体内观察到纳米颗粒在肝细胞中的高度积聚。该纳米粒的细胞毒性也明显低于含有多聚L-赖氨酸的纳米粒。因此，纳米粒有望用于肝脏特异性利巴韦林的低细胞毒性治疗慢性丙型肝炎。
Ribavirin is widely used in several types of combination chemotherapy for the treatment of chronic hepatitis C. In order to deliver ribavirin to the liver and reduce its side effects, we previously prepared ribavirin monophosphate (RMP)-loaded nanoparticles consisting of a mixture of poly(D,L-lactic acid), arabinogalactan-poly(L-lysine) conjugate, and iron (III) ions. In this study, the nanoparticles were developed in the absence of poly(L-lysine) to avoid cytotoxicity. The nanoparticles were successfully prepared from a mixture of poly(D,L-lactic acid) with terminal amino group(s) and arabinogalactan-poly(L-glutamic acid) conjugate. RMP was stably loaded in the nanoparticles and was gradually released from the nanoparticles under physiological conditions. Furthermore, high accumulation of the nanoparticles in hepatic cells was observedin vitroandin vivo. The nanoparticles also exhibited significantly lower cytotoxicity than that exhibited by those containing poly(L-lysine). Thus, the nanoparticles are expected to be useful in liver-specific ribavirin delivery with low cytotoxicity for the treatment of chronic hepatitis C.