Verma Prerna, Meher Jaya Gopal, Asthana Shalini, Pawar Vivek K, Chaurasia Mohini, Chourasia Manish K
a Pharmaceutics Division , CSIR-Central Drug Research Institute , Lucknow , India and.
b Amity Institute of Pharmacy, Amity University , Lucknow , India.
Drug Deliv. 2016;23(2):479-88. doi: 10.3109/10717544.2014.920430. Epub 2014 Jun 5.
Nanoemulsions (NE) are one of the robust delivery tools for drugs due to their higher stability and efficacy.
The purpose of present investigation is to develop stable, effective and safe NE of docetaxel (DTX).
Soybean oil, lecithin, Pluronic F68, PEG 4000 and ethanol were employed as excipients and NEs were prepared by hot homogenization followed by ultra-sonication. NEs were optimized and investigated for different in vitro and in vivo parameters viz. droplet size, poly dispersity index, charge; zeta potential, drug content and in vitro drug release, in vitro cytotoxicity, in vitro cell uptake and acute toxicity. Transmission electron microscopy was performed to study morphology and structure of NEs. Stability studies of the optimized formulation were performed.
Droplet size, poly dispersity index, zeta potential, drug content and in vitro drug release were found to be 233.23 ± 4.3 nm, 0.24 ± 0.010, -43.66 ± 1.9 mV, 96.76 ± 1.5%, 96.25 ± 2.1%, respectively. NE F11 exhibited higher cell uptake (2.83 times than control) and strong cytotoxic activity against MCF-7 cancer cells (IC50; 13.55 ± 0.21 µg/mL at 72 h) whereas no toxicity or necrosis was observed with liver and kidney tissues of mice at a dose of 20 mg/kg. Transmission electron microscopy ensured formation of poly-dispersed and spherical droplets in nanometer range. NE F11 (values indicated above) was selected as the optimized formulation based on the aforesaid parameters.
Conclusively, stable, effective and safe NE was developed which might be used as an alternative DTX therapy.
纳米乳剂（NE）因其较高的稳定性和有效性，是一种强大的药物递送工具。
本研究的目的是开发稳定、有效且安全的多西他赛（DTX）纳米乳剂。
以大豆油、卵磷脂、泊洛沙姆F68、聚乙二醇4000和乙醇为辅料，通过热均质化后超声处理制备纳米乳剂。对纳米乳剂进行优化，并研究其不同的体外和体内参数，即液滴大小、多分散指数、电荷、zeta电位、药物含量和体外药物释放、体外细胞毒性、体外细胞摄取和急性毒性。进行透射电子显微镜检查以研究纳米乳剂的形态和结构。对优化后的制剂进行稳定性研究。
液滴大小、多分散指数、zeta电位、药物含量和体外药物释放分别为233.23±4.3nm、0.24±0.010、-43.66±1.9mV、96.76±1.5%、96.25±2.1%。纳米乳剂F11表现出更高的细胞摄取（是对照的2.83倍）和对MCF-7癌细胞强烈的细胞毒性活性（72小时时的IC50；13.55±0.21μg/mL）；而在20mg/kg的剂量下未观察到小鼠肝脏和肾脏组织的毒性或坏死现象。透射电子显微镜检查确保了在纳米范围内形成多分散的球形液滴。基于上述参数，选择纳米乳剂F11（上述值）作为优化后的制剂。
最终，开发出了稳定、有效且安全的纳米乳剂，其可作为多西他赛疗法的替代方案。
