Application of the double emulsion prepared by membrane-emulsification technique for drug delivery system

研制了一种用于肝动脉注射化疗肝癌的油包水乳状液（W/O/W）。该乳液由碘化罂粟籽油（IPSO）微滴包裹大量溶解表阿霉素的水溶液组成。采用蓖麻油聚缩合脂肪酸聚甘油酯和聚氧乙烯60硬脂酸酯（氢化蓖麻油经环氧乙烷处理，摩尔比为1:60）两种表面活性剂来获得乳状液的足够稳定性：在室温下保存至少40天，没有观察到油和水的分离和IPSO微滴大小的变化。通过一系列的实验表明，由直径为70 μ m的IPSO微滴组成的W/O/W，在10 ml的内外水相中加入60 mg表柔比星，制备的W/O/W具有稳定性和有效性，适合临床应用。采用W/O/W法对24例肝切除术后肝癌复发患者进行肝动脉注射化疗。未见因油栓塞或抗癌药物引起的致命不良反应。复发后3年和5年的累计生存率分别为50%和24%。4个及以上结节患者3年累计生存率为50%。

We newly prepared a water-in-oil-in-water emulsion (W/O/W) for hepatic arterial injection chemotherapy for hepatocellular carcinoma (HCC). The emulsion consisted of iodinated poppy-seed oil (IPSO) microdroplets enclosing numerous vesicles of aqueous solution dissolving epirubicin. Two kinds of surfactant such as polyglycerol esters of polycondensed fatty acids of castor oil and polyoxyethlene 60 stearate (hydrogenated castor oil treated with ethylene oxide, 1 : 60, molar ratio) were used to attain adequate stability of the emulsion : separation of the oil arid water and changes in the size of IPSO microdroplets were not observed at least 40 days when stored in a vial at room temperature. From a series of experiments, it has been revealed that W/O/W which consists of IPSO microdroplets with a diameter of 70 mum and is prepared with 60 mg of epirubicin in total 10 ml of internal and external aqueous phase is applicable in clinical use because of its stability and efficacy. Using the W/O/W, we repeated hepatic arterial injection chemotherapy for 24 patients bearing recurrent HCC which occurred after hepatectomy. No fatal adverse effect originated in oil embolism or due to anticancer agent was encountered. The 3- and 5-year cumulative survival rates from the time of recurrence were 50 and 24%. As for the patients with four or more nodules, the 3-year cumulative survival rate was 50%.