目的 制备黄芩苷脂质体凝胶（baicalin liposomes gels，Bai-Lip-Gels），进行体外质量评价，并考察其治疗轻、中度痤疮的疗效。方法 首先采用单因素试验，以包封率、粒径为评价指标来考察处方工艺对脂质体制备的影响。其次，利用各因素与包封率之间的相关性选出影响脂质体制备的显著因素，并运用Box-Behnken设计-响应面法进一步优化处方工艺。然后制备Bai-Lip-Gels，采用流变学进行表征，对其稳定性进行初步考察，并通过透析袋释药试验和离体皮肤透皮试验考察Bai-Lip-Gels的释药性能。最后，对Bai-Lip-Gels进行兔耳痤疮的药效学评价。结果 成功制备黄芩苷脂质体（baicalin liposomes，Bai-Lip），其包封率为63.9%；在透射电子显微镜（TEM）下观察可见脂质体呈规则球形，结构完整，分散均匀；其粒径为（212.300±0.424）nm，多分散性指数（polydispersity index，PDI）为0.217±0.012，Zeta电位为（-32.4±0.9）mV，制备的Bai-Lip稳定。制备的Bai-Lip-Gels流变学性质稳定，在4℃冷藏贮存稳定性良好。离体皮肤透皮试验结果表明，Bai-Lip-Gels在18 h内单位面积累积渗透量（Q₁₈）为（81.38±2.81）μg/cm²，高于黄芩苷混悬剂凝胶（baicalin suspension gels，Bai-Sus-Gels）［Q₁₈为（43.03±2.14）μg/cm²］，并对Bai-Lip-Gels和Bai-Sus-Gels的释放曲线进行了方程拟合，Bai-Lip-Gels体外经皮渗透符合一级方程，Bai-Sus-Gels经皮渗透符合零级方程。初步药效学试验表明，在给药治疗后，组织病理染色结果可知，Bai-Lip-Gels组的疗效显著，主要体现在减轻角质化程度、局部组织充血、炎性程度等方面。从兔耳痤疮模型血清中肿瘤坏死因子α、白细胞介素1β、白细胞介素6、白细胞介素8分泌的影响发现，Bai-Lip-Gels能显著降低兔耳痤疮的炎症因子水平，且疗效优于阳性对照组阿达帕林凝胶。结论 制备的Bai-Lip-Gels用于兔耳痤疮治疗，能有效减轻角质化程度，减轻局部组织充血，降低炎症因子水平，为治疗轻、中度炎症性痤疮提供制剂开发的依据。

Objective To prepare baicalin liposomes gels (Bai-Lip-Gels), evaluate its quality in vitro, and investigate its efficacy in treating mild and moderate acne. Methods Firstly, a single factor test was used to investigate the influence of the formulation process on the preparation of liposomes with the encapsulation efficiency and particle size as evaluation indicators. Secondly, the correlation between each factor and the encapsulation efficiency was used to select the significant factors affecting the preparation of liposomes, and then, the Box-Behnken effect surface method was used to further optimize the prescription process. Moreover, Bai-Lip-Gels was prepared, and characterized by rheology, and its stability was preliminarily investigated, and the drug release of Bai-Lip-Gels was investigated through the dialysis bag release test and the in vitro skin transdermal test performance. Finally, the pharmacodynamics of Bai-Lip-Gels was evaluated for rabbit ear acne. Results The baicalin liposomes (Bai-Lip) were successfully prepared, with an encapsulation efficiency of 63.9%; Under the transmission electron microscope, the liposomes were in a regular spherical shape, with complete structure and uniform dispersion. The particle size was (212.300 ±0.424) nm, polydispersity index (PDI) was 0.217 ±0.012, Zeta potential was (-32.4 ±0.9) mV, and the prepared Bai-Lip was stable. The prepared Bai-Lip-gels had stable rheological properties and good storage stability at 4℃. The results of in vitro skin permeation test showed that the cumulative permeation per unit area in 18 h (Q₁₈) of Bai-Lip-Gels was (81.38 ±2.81) μg/cm², which was higher than Q₁₈ of baicalin suspension gels (Bai-Sus-Gels) which was (43.03 ±2.14) μg/cm², and the release curve of Bai-Lip-Gels and Bai-Sus-Gels was fitted with equations. The permeation of Bai-Lip-Gels in vitro conformed to the first-order equation, and the transdermal permeation of Bai-Sus-Gels penetration conformed to the zero-order equation. Preliminary pharmacodynamic tests showed that the therapeutic effect of the Bai-Lip-Gels group was significant after administration treatment by histopathological staining, which was mainly reflected in the reduction of keratinization, local tissue congestion, and inflammation. From the effects of TNF-α, IL-1β, IL-6, and IL-8 secretion in the serum of rabbit ear acne model, it is found that Bai-Lip-Gels significantly reduced the level of inflammatory factors in rabbit ear acne, and the curative effect was better than Adapalene gel group.Conclusion The preparation of Bai-Lip-Gels for the treatment of rabbit ear acne can effectively reduce the degree of keratinization, relieve local tissue congestion, and reduce the level of inflammatory factors, which provides a basis for the development of preparation for the treatment of mild and moderate inflammatory acne.

R283.6

2020年四川省科技创新苗子工程培育及小发明小创造项目；2020年江安县级科技计划项目