文献类型：期刊文献

英文题名：A Novel Drug Delivery Carrier Comprised of Nimodipine Drug Solution and a Nanoemulsion: Preparation, Characterization, in vitro, and in vivo Studies

作者：Huang, Saixu[1,2,3];Huang, Zhiyong[1,2,3];Fu, Zhiqin[3];Shi, Yamin[3,4];Dai, Qi[1,2];Tang, Shuyan[3];Gu, Yongwei[3];Xu, Youfa[3];Chen, Jianming[3,4];Wu, Xin[3];Ren, Fuzheng[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Minist Educ, Shanghai, Peoples R China;[3]Shanghai Weier Biol Med Sci & Technol Co Ltd, 358 Tian Chen Rd, Shanghai 201799, Peoples R China;[4]Fujian Univ Tradit Chinese Med, Dept Pharm, Fuzhou, Fujian, Peoples R China

年份：2020

卷号：15

起止页码：1161

外文期刊名：INTERNATIONAL JOURNAL OF NANOMEDICINE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000514170300001)】；

基金：This study was supported by Shanghai Key Laboratory of New Drug Design (Grant No. 17DZ2271000), the National Natural Science Foundation of China (NO. 81772749), Shanghai Rising-Star Program (NO. 18QB1400400), Shanghai Qingpu District Industry-University-Research Cooperation Development Fund Project (QIUR 2019-5), and Shanghai Science and Technology Project of Little Giant (1902HX76600).

语种：英文

外文关键词：nimodipine; nanoemulsion; pharmacokinetics; MCAO; LD50

摘要：Purpose: Nimodipine (NIMO) is used clinically to treat ischemic damage resulting from subarachnoid hemorrhage. However, clinical application of NIMO is limited by poor aqueous solubility and low safety. To overcome these limitations, a novel two-vial NIMO-loaded nanoemulsion (NIMO-TNE) was designed in this study. Methods: NIMO-TNE was prepared by mixing a nimodipine-polyethylene glycol 400 (NIMO-PEG400) solution and a commercially available 20% injectable blank nanoemulsion (BNE). Drug distribution in NIMO-TNE, physical stability, and dilution stability were evaluated in vitro, and pharmacokinetics and pharmacodynamics were evaluated in vivo. Safety was assessed using the hemolysis test and the intravenous irritation test, and acute toxicity of NIMO-TNE was compared with that of commercial Nimotop injection. Results: Drug loading (DL) in NIMO-TNE was enhanced 5-fold compared with that in Nimotop injection. The mean particle size of NIMO-TNE was 241.53 +/- 1.48 nm. NIMO-TNE and NIMO-TNE diluted in 5% glucose injection and 0.9% sodium chloride was stable for a sufficient duration to allow for clinical use. In addition, NIMO-TNE exhibited a similar pharmacokinetic profile and similar brain ischemia reduction in a rat middle cerebral artery occlusion (MCAO) model compared to Nimotop injection. Furthermore, NIMO-TNE did not induce hemolysis at 37 degrees C, and NIMO-TNE induced less intravenous irritation than Nimotop injection. Moreover, NIMO-TNE could be injected at a 23-fold higher dose than the LD50 of Nimotop injection with no obvious toxicity or side effects. Conclusion: NIMO-TNE is a promising formulation suitable for intravenous injection, is easy to prepare, and exhibits excellent safety.