经去氧胆酸钠修饰的白桦脂酸醇质体的制备及其体外透皮效果研究

Study on preparation and in vitro transdermal penetration of betulinic acid ethosomes modified by sodium deoxycholate

目的制备并优化白桦脂酸(BA)-去氧胆酸钠(SDC)修饰醇质体处方,并考察其作为BA经皮给药载体的渗透特性。方法采用乙醇注入法制备BA-SDC修饰醇质体,以包封率作为评价指标,采用正交试验法优化该醇质体处方,并考察其形态及粒径;采用Franz扩散池进行体外透皮吸收实验,比较BA-SDC修饰醇质体与脂质体、普通醇质体的经皮累积渗透量及渗透速率差异。结果优化后BA-SDC修饰醇质体最佳处方:大豆卵磷脂、SDC和BA的质量比为18∶1∶1,乙醇体积分数为35%。按优化后处方制得的BA-SDC修饰醇质体的平均包封率为(93.8±1.6)%,平均粒径为(102.3±3.6)nm;体外透皮12 h的累积透过量为(99.62±9.44)μg/cm2,分别达到了普通醇质体、脂质体和10%异丙醇饱和溶液的1.67、3.85和8.33倍。结论 SDC修饰醇质体包封率高,促进BA透皮吸收的效果明显,是BA最有前景的透皮给药剂型之一。

Objective To prepare and optimize the prescription of betulinic acid （BA） ethosomes modified by sodium deoxycholate （SDC） and then to investigate its transdermal penetration as carrier of BA. Methods The BA ethosomes modified by SDC were prepared by the ethanol injection method. The encapsulation efficiency （EE） was considered as the evaluation index to optimize the prescription of the ethosomes by orthogonal design, and the shape and particle size of the optimized ethosomes were analyzed. The in vitro transdermal absorption of BA was evaluated using Franz diffusion cells. The accumulated permeation amounts and permeation rate of liposomes, ethosomes, and BA ethosomes modified by SDC were compared. Results The best formulation consisted of soybean lecithin-SDC-BC （1 8 ： 1 ： 1） and 35% ethanol. The average EE and the particle size were （93.8 ± 1.6）% and （102.3 ± 3.6） nm, respectively. The accumulated permeation amount ofBA ethosomes modified by SDC in 12 h was （99.62 ± 9.44） μg/cm2, which was 1.67, 3.85, and 8.33 times ofethosomes, liposomes, and satuated solution containing 10% isopropanol, respectively. Conclusion The BA ethosomes, modified by SDC with high EE, obviously enhance the percutaneous absorption of BA and might be one of the most perspective percutaneous preparations. Key words：