LI Jiang-gai, WANG Yan, SONG Chun-jing, TANG Wen-jie, BAI Xin-shu, WANG Peng, ZHAI Yu-xin
Objective: To explore and optimize the formulation process of berberine liquid crystal cream, evaluate its physicochemical properties, sensory performance, therapeutic effect and potential mechanism for rabbit ear acne models, so as to provide theoretical basis for the development of new topical anti-acne preparations. Methods: Taking the dosages of emulsifiers (cetearyl glucoside, glyceryl monostearate and cetearyl alcohol) as key factors, the central composite design-response surface methodology (CCD-RSM) combined with analytic hierarchy process-inter-class correlation coefficient (AHP-ICC) composite weighting method was used to optimize the formulation. The comprehensive score of liquid crystal structure, stability and sensory performance was used as the evaluation index to determine the optimal formula. The oleic acid-induced rabbit ear acne model was established, and the animals were divided into a blank group, a model group, a low-dose berberine liquid crystal cream group, a medium-dose berberine liquid crystal cream group and a high-dose berberine liquid crystal cream group. After 3 weeks of intervention, the pathological changes of rabbit ear tissues were observed, and the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) in the tissues were detected to evaluate the therapeutic efficacy. Results: After process optimization and screening, the optimal formulation of berberine liquid crystal cream was determined as follows: cetearyl glucoside 4 g, glyceryl monostearate 1.5 g, cetearyl alcohol 3 g. The prepared berberine liquid crystal cream was a pale yellow fine ointment with a pH value of 5.61, showing good heat resistance, cold resistance and centrifugal stability. Sensory evaluation indicated that it had strong moisturizing property, was easily absorbed, and non-sticky. Pharmacodynamic experiments showed that compared with the model group, all dose groups of berberine liquid crystal cream could improve epidermal hyperplasia, follicular keratotic plugging and inflammatory cell infiltration of rabbit ears to different extents, with the high-dose group showing the most significant effect. Moreover, it could significantly down-regulate the gene expression levels of IL-1β, IL-6, IL-8 and TNF-α in rabbit ear tissues. Conclusion: Berberine liquid crystal cream can significantly reduce follicular keratotic plugging and inflammatory cell infiltration, and its inhibitory effect on inflammatory factors such as IL-1β, IL-6, IL-8 and TNF-α in rabbit ear tissues is dose-dependent, with the high-dose group exhibiting the most prominent therapeutic effect.