Zeng Liya, Zhang Yalin
a Key Laboratory of Plant Protection Resources and Pest Management, Ministry of Education , College of Plant Protection, Northwest A&F University , Yangling , China.
Pharm Dev Technol. 2017 May;22(3):399-408. doi: 10.1080/10837450.2016.1219915. Epub 2016 Sep 8.
This study focused on developing a self-nanoemulsifying drug delivery system (SNEDDS) containing bioactive surfactants under an efficient screening approach for overcoming problems associated with the delivery of norcantharidin (NCTD), a high dose chemotherapy agent having pH dependent solubility. Preliminary screening was implemented to select proper components combination. Besides the solubility of NCTD in the oil phase, emulsifying efficiency, droplet size and size distribution were also employed to select components of the SNEDDS. Moreover, the influence of surfactant and co-surfactant on the interfacial tension and droplets of nanoemulsions were investigated to further understand the mechanism of spontaneous emulsification. Co-surfactant addition promoted the emulsification via reducing the water/oil interfacial tension and viscosity. Ternary phase diagrams were constructed to investigate the phase behavior and designate the optimum systems. The alternative formulations were characterized for cloud point, dilution robustness, droplet size, polydispersity index (PDI) and transmission electron microscopy (TEM). In vitro dissolution study showed that the dissolution rate of optimized formulation (NCTD 10 mg/g, EO 50 wt.%, Cremophor EL 35 wt.%, ethylene glycol 15 wt.%) was slower than drug suspension under the same conditions, confirming that the developed SNEDDS formulation would exhibit sustained release potential.
本研究聚焦于开发一种包含生物活性表面活性剂的自纳米乳化药物递送系统（SNEDDS），采用高效筛选方法以克服与去甲斑蝥素（NCTD）递送相关的问题，NCTD是一种具有pH依赖性溶解度的高剂量化疗药物。进行了初步筛选以选择合适的组分组合。除了NCTD在油相中的溶解度外，还利用乳化效率、液滴大小和尺寸分布来选择SNEDDS的组分。此外，研究了表面活性剂和助表面活性剂对纳米乳液界面张力和液滴的影响，以进一步了解自发乳化的机制。添加助表面活性剂通过降低水/油界面张力和粘度促进了乳化。构建了三元相图以研究相行为并确定最佳体系。对替代配方进行了浊点、稀释稳定性、液滴大小、多分散指数（PDI）和透射电子显微镜（TEM）表征。体外溶出研究表明，在相同条件下，优化配方（NCTD 10 mg/g，EO 50 wt.%，聚氧乙烯蓖麻油EL 35 wt.%，乙二醇15 wt.%）的溶出速率比药物混悬液慢，证实所开发的SNEDDS配方具有缓释潜力。
