Development of multiple emulsion to deliver drugs

本研究选择w/o/w复合乳剂作为水溶性药物的载体，对其制备、药性评价及在给药系统（DDS）中的应用进行了研究。对于复合乳液的油相，采用油醇与植物油的混合油或肉豆蔻酸异丙酯的混合油来减小油相与水相的比重差异。HCO-40、HCO-50和Pluronic F-88分别作为疏水性和亲水性表面活性剂。水溶性药物包埋采用万古霉素、阿糖胞苷、阿霉素、ACNU。采用搅拌或膜乳化法制备多种乳剂。两种方法制备的乳状液在4个硫化氢的温度下均保持稳定。两种方法均可控制复合乳液的粒径。特别是膜法制备的复合乳液颗粒分布均匀。然而，用这种方法制备倍率高、倍率高的乳剂耗时长。虽然不同产品的包封效率和药物的释放特性不同，但它们可以通过复合乳剂的配方和制剂来控制。静脉注射包裹万古霉素的复合乳剂（粒径为3 μ m），可延长万古霉素的血药浓度。将包埋阿糖胞苷的粒径为3 μ m和30 μ m的多乳状液注入腹腔，分别用于肿瘤淋巴转移和腹膜癌的治疗。将包埋多柔比星的粒径为30 μ m的多柔比星乳液注入怀wak256大鼠肝动脉，将粒径为3 μ m的多柔比星乳液注入怀AH109A大鼠门静脉，均可延长处理组的存活时间。在脑膜胶质瘤患者鞘内注射包埋ACNU的复合乳剂，可延长治疗组的生存时间。研究结果表明，复合乳剂可作为水溶性药物的载体和药物的缓释。因此，可以通过控制乳液的粒径来应用于DDS。少

In this study, we selected the w/o/w multiple emulsion as a carrier of water-soluble drugs and studied on preparation, evaluation of pharmaceutical properties and applications for drug delivery system (DDS). For the oily phase of multiple emulsion, an oil mixture of Lipiodol and vegetable oil or isopropyl myristate were used to minimize the difference in specific gravity between oily phase and aqueous phase. HCO-40 or HCO-50 and Pluronic F-88 were used as hydrophobic and hydrophilic surfactants, respectively. For entrapping water-soluble drugs, vancomycin, cytarabine, doxorubicin and ACNU were used. Multiple emulsions were prepared with stirring or membrane emulsification methods.Multiple emulsions prepared by both methods were stable during storage at 4ﾟC.Particle size of the multiple emulsion was controlled by both methods. Especially, particle distribution of multiple emulsion prepared with membrane method showed homogeneousness. It however took too much time to prepare much multipl … More e emulsion in this method. Although the entrapment efficiency and the release property of drug were different among products, they could be controlled by formulations and preparations of the multiple emulsion.When the multiple emulsion (particle size being 3 mum) entrapping vancomycin was injected intravenously, the serum concentration of the drug was prolonged. When the multiple emulsions entrapping cytarabine whose particle sizes were 3 and 30 mum injected intraperitoneally, these emulsions were useful for treatments of lymphatic metastasis of cancer and peritoneal carcinomatosis, respectively. When the multiple emulsion entrapping doxorubicin, whose particle size was 30 mum, was injected into hepatic artery of rat bearing Waker 256, and when the emulsion whose particle size was 3 mum, was injected into the portal vein of rat bearing AH109A,survival times of the treated groups were prolonged. When the multiple emulsion entrapping ACNU was injected intrathecally to the meningeal gliomatosis, the survival time of the treated group was prolonged.The results of this study showed that the multiple emulsion was useful for a carrier of water-soluble drugs and sustained release of drugs. Therefore it can be applied to DDS by controlling the particle size of the emulsion. Less