鱼藤酮纳米脂质载体及其修饰物在大鼠体内的分布

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摘要［摘要］目的: 探讨聚乙二醇(polyethylene glycol，PEG)修饰后的鱼藤酮纳米脂质载体(rotenone loaded nanostructured lipid carriers, RNLC)在大鼠体内的分布。方法: 取SD大鼠123只，其中21只随机分为3组，每组7只，分别皮下注射鱼藤酮溶液、RNLC、PEG修饰的鱼藤酮纳米脂质载体(PEGRNLC)，在不同时间点取尾静脉血；其余102只SD大鼠随机分为17组，5组皮下注射鱼藤酮溶液，12组分别皮下注射RNLC(6组)和PEGRNLC(6组)，在不同时间点取各种组织；采用HPLC法检测血浆和组织样品中鱼藤酮的含量，观察并比较大鼠体内的分布。结果：鱼藤酮溶液在血液中达峰时间(Tmax)为4 h，在各组织分布的曲线下面积(AUC)由高到低依次为肾、肝、脑、脾、心、肺。RNLC和PEGRNLC在血液中的Tmax为8 h，AUC分别为鱼藤酮溶液35.99、42.03倍；RNLC在各组织分布的AUC由高到低分别为脑、肝脏、肾、心、脾、肺；与RNLC相比，PEGRNLC在脑组织(黑质、纹状体)中的分布明显升高，在外周组织中的分布均减少。结论： PEGRNLC能增加鱼藤酮在纹状体和黑质中的分布，进一步增强了RNLC的脑靶向效应。

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关键词 ：鱼藤酮, 纳米脂质载体, 聚乙二醇修饰, 曲线下面积, 脑靶向

Abstract：［Abstract］Objective： To observe pharmacokinetical characterization of rotenone loaded nanostructured lipid carriers (RNLC) modified by polyethylene glycol(PEG) in rats. Methods：One hundred and twentythree SD rats were used in the serial tests. Twentyone rats were divided into three groups, each group were injected with rotenone solution, RNLC and PEG modified rotenone nanostructured lipid carriers (PEGRNLC), respectively. Blood were collected at different time points.The remaining 102 SD rats were randomly divided into 17 groups, 5 groups received subcutaneous injection of rotenone solution, 12 groups were given subcutaneous injection of RNLC(6 groups) and PEGRNLC(6 groups), respectively. Tissues of interests were harvested at different time points. HPLC was used to determine and the distribution of rotenone in blood and tissues of different groups were evaluated. Results：The AUC of rotenone solution in tissues from high to low in order was kidneys, liver, brain, spleen, heart and lung. Tmax of rotenone solution was 4 h in blood, while it was 8 h of RNLC and PEGRNLC. The AUC of RNLC and PEGRNLC was 35.99 and 42.03 times higher than rotenone solution respectively. The AUC of RNLC in tissues from high to low in order was brain, liver, kidneys, heart spleen, and lung. The contention of PEGRNLC in tissues was significantly increased in brain (substantia nigra and striatum) and decreased in the peripheral issues. Conclusion：PEGRNLC could increase the contention of rotenone in the striatum and substantia nigra, which further enhanced brain targeting of RNLC.

收稿日期: 2016-04-20

作者简介: 李亚南（1986—），女，江苏如皋人，硕士，药师，主要从事临床药学的研究。

引用本文:

李亚南，毛全高. 鱼藤酮纳米脂质载体及其修饰物在大鼠体内的分布[J]. 江苏大学学报:医学版, 2016, 26(04): 346-351,366. LI Ya-nan, MAO Quan-gao. Pharmacokinetics of rotenone loaded nanostructured lipid carriers and its modifiers in rats. Journal of Jiangsu University(Medicine Edition), 2016, 26(04): 346-351,366.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2016/V26/I04/346

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