Chen Fang-Ning, Wang Xiu-Li, Xu Rui-Rui, Wang Xiao-Jie, Ruan Jing-Hua
Beijing University of Chinese Medicine Beijing 102488, China.
College of Bioengineering,Beijing Polytechnic Beijing 100176, China.
Zhongguo Zhong Yao Za Zhi. 2022 May;47(9):2449-2456. doi: 10.19540/j.cnki.cjcmm.20210323.303.
The optimal prescription of tanshinone Ⅱ_A(TSN)-glycyrrhetinic acid(GA) solid lipid nanoparticles(GT-SLNs) was explored and evaluated in vivo and in vitro, and its effect on acne after oral administration was investigated. The preparation processing and prescription were optimized and verified by single factor and response surface methodology. The in vitro release of GA and TSN in GT-SLNs was determined by ultra-performance liquid chromatography(UPLC). The effect of GT-SLNs on acne was investigated by the levels of sex hormones in mice, ear swelling model, and tissue changes in sebaceous glands, and the pharmacokinetics was evaluated. The 24-hour cumulative release rates of GA and TSN in SLNs were 65.87%±5.63% and 36.13%±2.31% respectively. After oral administration of GT-SLNs and the mixture of GA and TSN(GT-Mix), the AUC_(0-t) and AUC_(0-∞) of TSN in GT-SLNs were 1.98 times and 4.77 times those in the GT-Mix group, respectively, and the peak concentration of TSN in the GT-SLNs group was 17.2 times that in the GT-Mix group. After intragastric administration of GT-SLNs, the serum levels of testosterone(T) and the ratio of testosterone to estradiol(T/E2) in the GT-SLNs group significantly declined, and the sebaceous glands of mice were atrophied to a certain extent. The results demonstrated that obtained GT-SLNs with good encapsulation efficiency and uniform particle size could promote the release of GA and TSN. GT-SLNs displayed therapeutic efficacy on acne manifested by androgen increase, abnormal sebaceous gland secretion, and inflammatory damage.
探索并评估了丹参酮ⅡA（TSN）-甘草次酸（GA）固体脂质纳米粒（GT-SLNs）的最佳处方，并进行体内外研究，考察其口服给药对痤疮的影响。采用单因素法和响应面法对制备工艺和处方进行优化与验证。采用超高效液相色谱法（UPLC）测定GT-SLNs中GA和TSN的体外释放度。通过检测小鼠性激素水平、耳部肿胀模型以及皮脂腺组织变化研究GT-SLNs对痤疮的影响，并评估其药代动力学。SLNs中GA和TSN的24小时累积释放率分别为65.87%±5.63%和36.13%±2.31%。口服GT-SLNs及GA与TSN的混合物（GT-Mix）后，GT-SLNs中TSN的AUC_(0-t)和AUC_(0-∞)分别是GT-Mix组的1.98倍和4.77倍，GT-SLNs组中TSN的峰浓度是GT-Mix组的17.2倍。灌胃给予GT-SLNs后，GT-SLNs组小鼠血清睾酮（T）水平及睾酮与雌二醇比值（T/E2）显著下降，小鼠皮脂腺有一定程度萎缩。结果表明，所制备的GT-SLNs具有良好的包封率和均匀的粒径，可促进GA和TSN的释放。GT-SLNs对雄激素升高、皮脂腺分泌异常及炎症损伤所致痤疮具有治疗作用。
