College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
AAPS PharmSciTech. 2009;10(3):1058-64. doi: 10.1208/s12249-009-9295-1. Epub 2009 Aug 11.
In this study, a nanoemulsion (NE) system was investigated for intravenous delivery of lipophilic and venous irritant drugs. NEs were prepared to deliver diallyl trisulfide (DT) for systemic therapy of bacterial and fungal infection, egg phospholipid was chosen as the main emulsifier, and two co-emulsifiers were also incorporated, including Poloxamer 188 (P188) and Solutol HS 15 (S15). Soybean oil was used as the dispersed phases, forming stable DT NEs with small particle sizes. The venous irritation of DT NEs was evaluated by in vitro human umbilical cord endothelial cells (CRL 1730) compatibility model with the intracellular adenosine triphosphate (ATP) and guanosine triphosphate (GTP) concentrations as the indices. The intracellular ATP and GTP reduction changed with the incorporation of a variety of co-emulsifiers, which varied in a free DT concentration-dependent manner. It was deduced that the free DT concentrations of NEs containing co-emulsifiers were determined by the partition coefficient of DT between oil and surfactant buffer solution. In conclusion, NE was an appropriate delivery system for lipophilic and venous irritant drug, and optimization of the composition of emulsifiers was an effective method to alleviate the venous irritation of DT NEs.
在这项研究中，考察了一种纳米乳液（NE）系统，用于静脉内递送亲脂性和静脉刺激性药物。制备 NE 以用于治疗细菌和真菌感染的全身治疗，选择蛋黄磷脂作为主要乳化剂，并同时掺入两种辅助乳化剂，包括泊洛沙姆 188（P188）和 Solutol HS 15（S15）。大豆油被用作分散相，形成具有小粒径的稳定的 DT NE。通过体外人脐带内皮细胞（CRL 1730）相容性模型，以细胞内三磷酸腺苷（ATP）和三磷酸鸟苷（GTP）浓度作为指标，评价 DT NE 的静脉刺激性。随着各种辅助乳化剂的掺入，细胞内 ATP 和 GTP 的减少发生变化，这与游离 DT 浓度呈依赖性变化。推断含有辅助乳化剂的 NE 中的游离 DT 浓度由 DT 在油和表面活性剂缓冲溶液之间的分配系数决定。总之，NE 是亲脂性和静脉刺激性药物的合适递送系统，乳化剂组成的优化是减轻 DT NE 静脉刺激性的有效方法。
