柔性纳米脂质体双氯芬酸钠外用透皮吸收的效果

Percutaneous absorption of the flexible nanoliposomes in diclofenac sodium for external application

目的:观察双氯芬酸钠柔性纳米脂质体皮肤给药缓释系统体外透皮吸收情况。方法:验于2005-03/11在中南大学湘雅医院中西结合研究所完成。实验材料:双氯芬酸钠柔性纳米脂质体(中南大学化工研究所,将双氯芬酸钠制成纳米粒,并包封于卵磷脂及其有生物膜特性和功能的脂质体中,其粒径为30～100nm),扶他林(双氯芬酸钠)。实验分组:15只健康的SD大鼠按随机数字表法分为3组:质量分数为0.01的扶他林组、质量分数为0.05的外用双氯芬酸钠柔性纳米脂质体组和质量分数为0.1的外用双氯芬酸钠柔性纳米脂质体组,每组5只。将鼠皮装于Franz扩散池,角质层面向供给室,真皮层面向接受池,分别将质量分数为0.05的外用双氯芬酸钠柔性纳米脂质体25mg、质量分数为0.1的外用双氯芬酸钠柔性纳米脂质体12.5mg和质量分数为0.01的扶他林125mg(含双氯芬酸钠均为1.25mg)均匀涂布于大鼠皮肤角质层表面,分别于2,4,6,8,10,12h于接受池取样5mL,用0.45μm微孔滤膜过滤。滤液用生理盐水稀释至10mL,于276nm处测定吸光度值,扣除生理盐水的吸光度值后代入标准曲线,计算累积透过量和12h累积透过率,对比3种制剂经大鼠皮肤的体外透皮吸收差异。结果:质量分数为0.05,0.1的外用双氯芬酸钠柔性纳米脂质体组累积透过量、12h累积透过率均高于质量分数为0.01的扶他林组[12h累积透过率分别为(70.76±0.23)%,(75.2±0.32)%,(33.51±0.29)%],差异有显著性意义(t=317.17,232.54,P<0.01);质量分数为0.05的外用双氯芬酸钠柔性纳米脂质体组与质量分数为0.1的外用双氯芬酸钠柔性纳米脂质体组累积透过量、12h累积透过率差异无显著性意义(P>0.05)。结论:双氯芬酸钠柔性纳米脂质体能有效渗透皮肤组织。

AIM： To study the percutaneous absorption in vitro of the flexible nanoliposomes transdermal delivery system of diclofenac sodium （DM） for external application. METHODS： The experiment was completed in Institute of Combined Traditional Chinese and Western Medicine, Xiangya Hospital of Central South University from March to November in 2005. Experimental materials： flexible nanoliposomes of DS （Institute of Chemistry, Central South University, DA nanoparticles was coated with lecithin and liposome that possessed the characteristics and function of biomembrane, and the diameter of nanoparticles was 30-100 nm）, voltaren （DS）. Experimental grouping： Totally 15 healthy SD rats were randomly divided into 3 groups： the 0.05 quality fraction of the flexible nanoliposomes of DS for external application group, the 0.1 quality fraction of the flexible nanoliposomes of DS for external application group and the 0.01 quality fraction of the voltaren group, 5 rats for each group. Franz diffusion cell was adopted, rat horny layer towards supply division while dermis towards recipient division. Then the flexible nanoliposomes of DS for external application （the quality fraction was 0.05） 25 mg, the flexible nanoliposomes of DS for external application （the quality fraction was 0.1） 12.5 mg and the voltaren （the quality fraction was 0.01） 125 mg were respectively used to spread on the horny layer of the rats, containing 1.25 mg DS. Then 5 mL sample from recipient division was filtered by using the 0.45 μm micropore film on the 2^nd, 4^th, 6^th, 8^th, 10^th and 12^th hours. The filtrate was attenuated to 10 mL by physiologic saline and the absorbance on 276 nm was determined. Subtracting the absorbance of the physiologic saline, we used the standard curve to compute the accumulated transmit dose and the accumulated transmissivity of 12 hours. The percutaneous absorptions in vitro of three preparations were compared. RESULTS： The accumulated transmit dose and the accumulated transmissivity of 12 hours were higher in the flexible nanoliposomes of DS for external application groups than in the voltaren group, and the difference was significant [the accumulated transmissivity of 12 hours： （70.76±0.23）%, （75.2±0.32）%, （33.51±0.29）%, t =317.17, 232.54, P 〈 0.01]; The accumulated transmit dose and the accumulated transmissivity of 12 hours were not significantly deviated between the 0.05 quality fraction and the 0.1 quality fraction of the flexible nanoliposomes of DS for external application （P 〉 0.05）. CONCLUSION： The flexible nanoliposomes of DS for external application can penetrate through the skin effectively.