Sakaeda T, Hirano K
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
J Drug Target. 1995;3(3):221-30. doi: 10.3109/10611869509015949.
The potential usefulness of O/W lipid emulsions as injectable drug delivery systems for lipophilic drugs was examined using a model lipophilic drug, sudan II (clogP = 5.4) in the normal rats. The standard lipid emulsion composed of soybean oil and egg yolk phosphatides increased the blood concentration of sudan II after i.v. injection when compared with its solubilized solution by plasma. However, it was still lower than that of the oil particles, and the distribution of sudan II to liver, lungs, adipose tissue, heart, and muscle was not altered, and only that to brain and kidneys was decreased. Herein, the effect of extensive alterations in the lipid emulsion composition on the blood concentration and organ distribution of sudan II was examined in comparison with the standard formulation. Addition of cholesterol, use of pure egg yolk phosphatidylcholine, use of phospholipids with saturated alkyl chain, use of saturated long chain triglycerides, and use of saturated medium chain triglycerides were tested. The oil particles of all tested lipid emulsions were still located in plasma space, and use of saturated medium chain triglycerides was the most effective way to increase blood concentration of sudan II, resulting in higher distribution to liver, lungs, spleen, and brain. This was caused by the increase of the steady-state partition of sudan II to the oil particles, and not by alteration of their organ distribution clearance.
使用模型亲脂性药物苏丹II（logP = 5.4）在正常大鼠中研究了水包油型脂质乳剂作为亲脂性药物注射给药系统的潜在用途。与苏丹II的血浆增溶溶液相比，由大豆油和蛋黄磷脂组成的标准脂质乳剂在静脉注射后提高了苏丹II的血药浓度。然而，其血药浓度仍低于油相颗粒，且苏丹II在肝脏、肺、脂肪组织、心脏和肌肉中的分布未改变，仅在脑和肾脏中的分布减少。在此，与标准制剂相比，研究了脂质乳剂组成的广泛改变对苏丹II血药浓度和器官分布的影响。测试了添加胆固醇、使用纯蛋黄磷脂酰胆碱、使用具有饱和烷基链的磷脂、使用饱和长链甘油三酯以及使用饱和中链甘油三酯的情况。所有测试脂质乳剂的油相颗粒仍位于血浆中，使用饱和中链甘油三酯是提高苏丹II血药浓度的最有效方法，导致其在肝脏、肺、脾脏和脑中的分布增加。这是由于苏丹II在油相颗粒中的稳态分配增加所致，而非其器官分布清除率的改变。
