Preparation of Nanocrystals for Insoluble Drugs by Top-Down Nanotechnology with Improved Solubility and Bioavailability
Preparation of Nanocrystals for Insoluble Drugs by Top-Down Nanotechnology with Improved Solubility and Bioavailability
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采用自上而下的纳米技术制备难溶性药物纳米晶体，提高溶解度和生物利用度
DOI：
10.3390/molecules25051080
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发表时间：
2020-02
期刊：
影响因子：
4.6
通讯作者：
Aiping Zheng
中科院分区：
文献类型：
--
作者：
Xun Zhang;Zhiguo Li;Jing Gao;Zengming Wang;Xiang Gao;Nan Liu;Meng Li;Hui Zhang;Aiping Zheng
咪达唑仑是一种快速有效的苯二氮卓类药物，在世界范围内被广泛用作镇静剂。由于咪达唑仑在中性水溶液中的溶解性较差，其临床应用受到很大限制。纳米晶作为最有前途的难溶药物制剂之一，受到了世界各国的广泛关注。我们准备了一种稳定的纳米悬浮系统，几乎不会对肌肉产生刺激。所制得的咪达唑仑纳米晶(MDZ/NCS)的粒径为286.6±2.19 nm，在粒径减小的过程中，咪达唑仑的晶态没有发生变化，其溶出速度明显加快。药代动力学研究表明，MDZ/NCS的AUC0-t是咪达唑仑溶液(MDZ/S)的2.72倍，表明MDZ/NC注射剂的生物利用度高于MDZ/S。在惊厥发作后立即给予咪达唑仑，MDZ/NCS的ED50明显高于MDZ/S和DZP/S。这些结果表明，纳米晶显著影响咪达唑仑的溶出行为、药代动力学特性、抗惊厥作用和神经保护作用，并最终增强其体外和体内的疗效。
Midazolam is a rapidly effective benzodiazepine drug that is widely used as a sedative worldwide. Due to its poor solubility in a neutral aqueous solution, the clinical use of midazolam is significantly limited. As one of the most promising formulations for poorly water-soluble drugs,nanocrystals have drawn worldwide attention. We prepared a stable nanosuspension system that causes little muscle irritation. The particle size of the midazolam nanocrystals (MDZ/NCs) was286.6 ± 2.19 nm, and the crystalline state of midazolam did not change in the size reduction process.The dissolution velocity of midazolam was accelerated by the nanocrystals. The pharmacokinetics study showed that the AUC0–t of the MDZ/NCs was 2.72-fold (p < 0.05) higher than that of the midazolam solution (MDZ/S), demonstrating that the bioavailability of the MDZ/NC injection was greater than that of MDZ/S. When midazolam was given immediately after the onset of convulsions,the ED50 for MDZ/NCs was significantly more potent than that for MDZ/S and DZP/S. The MDZ/NCs significantly reduced the malondialdehyde content in the hippocampus of the seizures model rats and significantly increased the glutathione and superoxide dismutase levels. These results suggest that nanocrystals significantly influenced the dissolution behavior, pharmacokinetic properties,anticonvulsant effects, and neuroprotective effects of midazolam and ultimately enhanced their efficacy in vitro and in vivo.
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影响因子：
11.2
作者：
E. So;J. Penry
通讯作者：
E. So;J. Penry
DOI：
10.1615/critrevtherdrugcarriersyst.v28.i5.20
发表时间：
2011
影响因子：
2.7
作者：
Sandip S Chavhan;Kailash C. Petkar;K. Sawant
通讯作者：
Sandip S Chavhan;Kailash C. Petkar;K. Sawant
影响因子：
5.8
作者：
Deng, Jiexin;Huang, Leaf;Liu, Feng
通讯作者：
Liu, Feng
影响因子：
3.8
作者：
D. Marston;F. Besag;Colin D. Binnie;M. Fowler
通讯作者：
D. Marston;F. Besag;Colin D. Binnie;M. Fowler
影响因子：
5.6
作者：
Wirrell, Elaine C.
通讯作者：
Wirrell, Elaine C.