甘草酸载入普朗尼克F127/聚乙二醇1000维生素E琥珀酸酯混合纳米胶束的制备及对小鼠特应性皮炎的研究

Preparation of glycyrrhizic acid-loaded F127/TPGS mixed nanomicelles and its therapeutic effects on atopic dermatitis in mice

目的:研究甘草酸(glycyrrhizic acid,GL)载入普朗尼克F127/聚乙二醇1000维生素E琥珀酸酯(TPGS)混合纳米胶束(MMs)后对小鼠特应性皮炎(atopic dermatitis,AD)的治疗作用。方法:采用薄膜分散法制备GL-F127/TPGS-MMs,并对其粒径、包封率、形态等进行表征。用2,4-二硝基氯苯(2,4-dinitrochlorobenzene,DNCB)对雌性BALB/c小鼠建立特应性皮炎模型。小鼠分为9组:空白对照组、模型对照组、地塞米松组(30 mg·kg^(-1))、GL溶液低、中、高剂量组(25,50,100 mg·kg^(-1))、GL-F127/TPGS-MMs低、中、高剂量组(25,50,100 mg·kg^(-1))。灌胃给药14 d,检测小鼠血清免疫球蛋白E(IgE)水平、耳肿胀度、胸腺指数、脾脏指数、皮肤厚度、皮损组织病理变化等指标,评价GL-F127/TPGS-MMs对小鼠特应性皮炎的治疗效果。结果:与模型组比较,造模d 28 GL-F127/TPGS-MMs组皮损评分均显著降低(P<0.05)。灌胃给药14 d,与模型组比较,GL-F127/TPGS-MMs各剂量组小鼠IgE含量、耳肿胀度、胸腺指数、脾脏指数、皮损厚度显著降低(P<0.05或0.01)。通过观察皮损组织病理变化,模型对照组的表皮和真皮的厚度明显增加,GL-F127/TPGS-MMs治疗组的表皮和真皮厚度明显变薄。与GL溶液组相比,GL-F127/TPGS-MMs高剂量组小鼠AD病理变化明显改善,表皮增生、真皮炎性浸润和细胞内及细胞间的水肿程度明显减轻。结论:GL-F127/TPGS-MMs对小鼠特应性皮炎具有显著的治疗作用。

Objective:To investigate the effect of glycyrrhizic acid(GL)-loaded F127/TPGS-MMs in mice model of atopic dermatitis(AD).Methods:GL-F127/TPGS-MMs was prepared by thin film dispersion method and characterized by particle size,entrapment efficiency,drug loading and morphology.A AD model was induced by 2,4-dinitrochlorobenzene(DNCB)in female BALB/c mice.And then the mice were divided into 9 groups:normal control group,model group,dexamethasone positive group(30 mg·kg^(-1)),low(25 mg·kg^(-1)),medium(50 mg·kg^(-1))and high(100 mg·kg^(-1))doses of glycyrrhizic acid solution groups and GL-F127/TPGS-MMs group.After oral administration for 14 days,the mice’s serum level of IgE,ear swelling degree,thymus index,spleen index,skin thickness,and pathological changes of skin lesions were detected to evaluate the therapeutic effects of GL-F127/TPGS-MMs on AD in mice.Results:Compared with the model group,the skin lesion scores of the GL-F127/TPGS-MMs groups significantly decreased on the 28 th day of model establishment(P<0.05).After intragastric administration for 14 days,the levels of IgE,ear swelling degree,thymus index,spleen index and skin lesion thickness of mice in GL-F127/TPGS-MMs groups significantly decreased(P<0.05 or 0.01)compared with the model group.The thickness of the epidermis and dermis significantly increased in the model control group and significantly reduced in GL-F127/TPGS-MMs group according to the pathological changes of the skin lesions.Compared with the GL solution groups,the AD pathological changes of the mice in GL-F127/TPGS-MMs high-dose group were significantly improved,and the epidermal hyperplasia,dermal inflammatory infiltration,and intracellular and intercellular edema were significantly reduced.Conclusion:GL-F127/TPGS-MMs has a significant therapeutic effect on AD in mice.