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

被引:15
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
来源
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2020年 / 15卷
基金
中国国家自然科学基金;
关键词
nimodipine; nanoemulsion; pharmacokinetics; MCAO; LD50; LIPID NANOEMULSION; SOLID DISPERSION; ACUTE TOXICITY; FORMULATION; PHARMACOKINETICS; ACTIVATION; INJECTION; LIPOSOMES; APOPTOSIS; MCAO;
D O I
10.2147/IJN.S226591
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
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.
引用
收藏
页码:1161 / 1172
页数:12
相关论文
共 40 条
  • [1] Artificial neural networks in the optimization of a nimodipine controlled release tablet formulation
    Barmpalexis, Panagiotis
    Kanaze, Feras Imad
    Kachrimanis, Kyriakos
    Georgarakis, Emanouil
    [J]. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2010, 74 (02) : 316 - 323
  • [2] RAT MIDDLE CEREBRAL-ARTERY OCCLUSION - EVALUATION OF THE MODEL AND DEVELOPMENT OF A NEUROLOGIC EXAMINATION
    BEDERSON, JB
    PITTS, LH
    TSUJI, M
    NISHIMURA, MC
    DAVIS, RL
    BARTKOWSKI, H
    [J]. STROKE, 1986, 17 (03) : 472 - 476
  • [3] REQUIREMENT OF DNA TOPOISOMERASES FOR INVITRO CHROMATIN ASSEMBLY BY 3T6 MOUSE-CELL EXTRACTS
    CACERES, JF
    BLANGY, D
    GLIKIN, GC
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1989, 181 (02): : 531 - 537
  • [4] Formulation and evaluation of Nimodipine-loaded solid lipid nanoparticles delivered via lymphatic transport system
    Chalikwar, Shailesh S.
    Belgamwar, Veena S.
    Talele, Vivek R.
    Surana, Sanjay J.
    Patil, Mrunal U.
    [J]. COLLOIDS AND SURFACES B-BIOINTERFACES, 2012, 97 : 109 - 116
  • [5] An optimized two-vial formulation lipid nanoemulsion of paclitaxel for targeted delivery to tumor
    Chen, Lina
    Chen, Bingchen
    Deng, Li
    Gao, Baoan
    Zhang, Yuansheng
    Wu, Chan
    Yu, Nong
    Zhou, Qinqin
    Yao, Jianzhong
    Chen, Jianming
    [J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2017, 534 (1-2) : 308 - 315
  • [6] Nanostructured lipid carrier mediates effective delivery of methotrexate to induce apoptosis of rheumatoid arthritis via NF-κB and FOXO1
    Garg, Neeraj K.
    Tyagi, Rajeev K.
    Singh, Bhupinder
    Sharma, Gajanand
    Nirbhavane, Pradip
    Kushwah, Varun
    Jain, Sanyog
    Katare, Om Prakash
    [J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2016, 499 (1-2) : 301 - 320
  • [7] Acute toxicity and anticonvulsant activity of liposomes containing nimodipine on pilocarpine-induced seizures in mice
    Gayoso e Almendra Ibiapina Moreno, Lina Clara
    Ferro Cavalcanti, Isabella Macario
    Satyal, Prabodh
    Santos-Magalhaes, Nereide Stela
    Lins Rolim, Hercilia Maria
    Freitas, Rivelilson Mendes
    [J]. NEUROSCIENCE LETTERS, 2015, 585 : 38 - 42
  • [8] CALCIUM-CHANNEL BLOCKERS IN THE TREATMENT OF MIGRAINE
    GELMERS, HJ
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 1985, 55 (03) : B139 - B143
  • [9] Lipid nanoparticles enhance the absorption of cyclosporine A through the gastrointestinal barrier: In vitro and in vivo studies
    Guada, Melissa
    Lasa-Saracibar, Beatriz
    Lana, Hugo
    del Carmen Dios-Vieitez, Maria
    Blanco-Prieto, Maria J.
    [J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2016, 500 (1-2) : 154 - 161
  • [10] Injectable nimodipine-loaded nanoliposomes: Preparation, lyophilization and characteristics
    Guan, Tingting
    Miao, Yuqiang
    Xu, Lishuang
    Yang, Shenshen
    Wang, Jing
    He, Haibing
    Tang, Xing
    Cai, Cuifang
    Xu, Hui
    [J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2011, 410 (1-2) : 180 - 187