鞣花酸柔性纳米脂质体的制备工艺优化与体外透皮实验

Preparation Optimization and In Vitro Percutaneous Permeability Experiment of Flexible Nanoliposomes of Ellagic Acid

以包封率为指标,考察鞣花酸柔性纳米脂质体(EA-FNL)的最佳制备工艺,验证其透皮效果.采用薄膜分散法制备鞣花酸柔性纳米脂质体,采用高效液相色谱法检测鞣花酸柔性纳米脂质体的包封率,通过单因素实验考察表面活性剂的种类、卵磷脂与表面活性剂的质量比、卵磷脂与胆固醇的质量比、药物质量浓度、水化时间对包封率和粒径的影响.经Box-Behnken效应面法得到最优处方,测定其粒径,以大鼠腹部皮肤为材料,进行24 h透皮扩散实验.结果表明:在Box-Behnken响应面优化处方实验确定的最佳工艺中,卵磷脂与胆固醇的质量比为7.83∶1,脂质体制备水化时间为2.1 h,卵磷脂与吐温-20的质量比为2∶1,平均包封率为75.66%,粒径为(178.60±4.59)nm,聚合物分散性指数(PDI)为0.15±0.01,电位为(-30.60±0.92)mV,EA-FNL稳定性良好;EA-FNL 24 h累积透过量为9.54μg·cm^-2,24 h后皮肤滞留量为13.77μg·cm^-2;文中方法制备的鞣花酸柔性纳米脂质体包封率较高,粒径可控,在皮肤滞留量较高.

The optimum preparation technology of flexible nanoliposomes of ellagic acid(EA-FNL)was studied with encapsulation efficiency as index,and its transdermal effect was verified.EA-FNL was prepared by thin film dispersion,and the encapsulation efficiency of EA-FNL was determined by high performance liquid chromatography.The effects of the type of surfactant,the mass ratio of lecithin and surfactant,the mass ratio of lecithin and cholesterol,the concentration of medicine,and the hydration time on the encapsulation efficiency and the particle size were investigated by single factor test.The optimal prescription was obtained by the Box-Behnken response surface method,and the particle size was measured.A 24 htransdermal diffusion experiment was performed using rat abdominal skin as a material.The result shows that optimal prescription was:a mass ratio of lecithin to cholesterol 7.83∶1,the hydration time for liposome preparation 2.1 h,and the mass ratio of lecithin to Tween-202∶1.Under the optimal prescrition,the average encapsulation efficiency was 75.66%,particle size was(178.60±4.59)nm,the polymer dispersity index(PDI)was 0.15±0.01,the potential was(-30.60±0.92)mV,and the stability of EA-FNL was good.The cumulative transmittance of EA-FNL for 24 hwas 9.54μg·cm^-2,and the skin retention at 24 hwas 13.77μg·cm^-2.It reveals that EA-FNL prepared by this method has higher encapsulation efficiency,controllable particle size and high retention in skin.