盐酸米托蒽醌脂质体制备及其经皮吸收分布规律的研究

Preparation of Mitoxantrone Liposomes and Study on Its in vivo Distribution in Rats after Transdermal Delivery

目的研究盐酸米托蒽醌脂质体在体经皮给药的透皮规律。方法采用薄膜法制备盐酸米托蒽醌脂质体,测定其粒径、荷电性及包封率;以静脉注射盐酸米托蒽醌水溶液为对照,进行盐酸米托蒽醌脂质体大鼠在体经皮给药实验,用HPLC法测定药物在两组各组织、器官中的浓度,分析经时变化规律。并用3p97程序处理大鼠皮肤药时数据。结果盐酸米托蒽醌脂质体体积平均粒径为50.98nm,荷电性为-16.57mv,包封率可达100%;大鼠在体经皮给药,所得皮肤药-时曲线符合一室模型,2h皮肤中分布达高峰,峰浓度为(2.075±0.098)μg/g,药时曲线下面积为15.01μg·h/g;静脉注射给药,所得皮肤药-时曲线符合二室模型,药时曲线下面积为10.74μg·h/g,与经皮给药组相比,差异有统计学意义(P<0.05)。而其他组织、器官中的药物浓度均远低于对照。结论盐酸米托蒽酯脂质体皮肤局部给药可实现局部皮肤靶向,有望用于治疗恶性皮肤黑色素瘤。

Objective To investigate in viva distribution of the mitoxantrone （MIT） liposomes in SD rats after transdermal delivery. Methods The mitoxantrone liposomes were prepared by thin-film method. Particle size, particle distribution and δ-potential of colloid solution were obtained on laser scatterometer ; the encapsulation efficiency was measured by membrane diffusion technique. The time courses of mitoxantrone concentration in viva after the transdermal delivery of mitoxantrone liposomes were measured by HPLC assays and compared with the injection of mitoxantrone solution. Results The mean diameter of the MIT liposomes was 50. 98 nm, with the entrapping efficiency of 100%. The liposomes had perfect shape. A significantly higher amount of mitoxantrone was delivered in cutis after transdermal delivery of mitoxantrone liposomes, compared with the injection of mitoxantrone solution ; meanwhile, a significantly lower amount of mitoxantrone was delivered in plasma and other tissues after transdermal delivery of mitoxantrone liposomes, compared with the injection of mitoxantrone solution. Conclusion Transdermal delivery of mitoxantrone liposomes could be a potential therapy for cutaneous malignant melanoma.