复方甲氨蝶呤-氨茶碱水凝胶的制备及其药效学初步探究OA

Objective To optimize the formulation and preparation technology of compound methotrexate-aminophylline hydrogel,and explore its therapeutic effect on mice model of vulgaris psoriasis.Methods Single factor test and Box-Behnken response surface methodology were applied to optimize the formulation and preparation parameters.A total of 15 mice were randomly divided into three groups,among which one group was set as blank control group without any treatment.The other two groups were topically administered with 5%imiquimod(IMQ)cream on the left ear for 6 consecutive days to establish psoriasis-like skin lesion models,namely the psoriasis model group and the compound methotrexate-aminophylline hydrogel treatment group.The ear skin lesions of mice were observed,and the changes in ear thickness were recorded.HE staining was performed to observe the pathological changes of ear skin and small intestinal tissues.Western blotting was used to detect the protein expression levels of JAK1,STAT3 and STAT5 in ear skin tissues.Results The optimal formulation and preparation conditions of compound methotrexate-aminophylline hydrogel were as follows:Carbomer 940 2.04%,propylene glycol 21.49%,azone 2.85%,and the system pH was 7.0.In the compound methotrexate-aminophylline hydrogel group,the skin lesions of mice were significantly alleviated,the thickness of left ear and epidermal thickness were reduced,and the relative protein expression levels of JAK1,STAT3 and STAT5 in ear skin tissues were down-regulated.Conclusion The established hydrogel preparation process is relatively simple and demonstrates reproducibility.Compound methotrexate-aminophylline hydrogel has a good therapeutic effect on psoriasis mouse model,reducing skin inflammation,which may play a therapeutic role through JAK/STAT inflammatory signal pathway.