雷公藤甲素二元醇质体的制备及评价

Preparation and evaluation of triptolide binary ethosomes

目的制备包载雷公藤甲素(TP)的二元醇质体并考察其体外透皮性能。方法采用注入-探头式超声法制备TP二元醇质体,以粒径和包封率为评价指标,通过单因素试验和Box-Behnken响应面法优化TP二元醇质体的制备工艺,并对其进行表征,以改良的Franz扩散池研究其体外透皮吸收性能。结果TP二元醇质体制备工艺:TP投药量为8.3 mg,卵磷脂浓度为6.9 mg·mL^(-1),醇相用量为38.5%,二元醇比(乙醇∶丙二醇)为7∶3,胆卵比(胆固醇∶卵磷脂)为1∶5,制备温度为35℃,转速为600 r·min^(-1),水合时间为30 min,超声功率为200 W,制得的TP二元醇质体外观澄清透明,有淡蓝色乳光,平均粒径为(124.7±0.46)nm,PDI为(0.166±0.02),Zeta电位为(-14.7±0.47)mV,在4℃下稳定性较好;体外经皮给药24 h,普通醇质体、二元醇质体和TP乙醇水溶液中TP单位面积累积透过量分别为(549.99±47.97)、(751.62±27.38)、(957.71±40.20)μg·cm^(-2),且制备的二元醇质体与Higuchi模型拟合度较高。结论制备的TP二元醇质体粒径小且均一,易保存,具有良好的透皮吸收特性。

Objective To prepare binary ethosomes containing triptolide(TP)and determine its in vitro transdermal performance.Methods The injection-probe ultrasonic method was used to prepare TP binary ethosomes.The evaluation indicators included particle size and encapsulation efficiency.The single factor test and Box-Behnken response surface method were used to optimize the preparation of TP binary ethosomes.The modified Franz diffusion cells were used to determine its in vitro transdermal absorption.Results The preparation of TP binary ethosomes was as follows:the dosage of TP was 8.3 mg,the concentration of lecithin was 6.9 mg·mL^(-1),the proportion of alcohol was 38.5%,and the proportion of glycol(ethanol∶propylene glycol)was 7∶3,the ratio of cholesterol∶lecithin was 1∶5,the preparation temperature was 35℃,the rotation speed was 600 r·min^(-1),the hydration lasted 30 min,and the ultrasonic power was 200 W.The appearance of the TP binary ethosomes was clear and transparent with light blue opalescence.The particle size was(124.7±0.46)nm,PDI was(0.166±0.02),Zeta potential was(-14.7±0.47)mV,and it was stable at 4℃.After the 24 h transdermal administration in vitro,the cumulative permeation per unit area of TP per unit area of ordinary alcohol,glycol,and TP ethanol aqueous solution was(549.99±47.97),(751.62±27.38),and(957.71±40.20)μg·cm^(-2).The prepared binary ethosomes fit well with the Higuchi model.Conclusion The TP binary ethosomes prepared have small particle size and uniformity and good transdermal absorption characteristics.