分心木水提物可溶性微针的制备及其对小鼠皮肤溃疡的治疗效果研究

Study on the Preparation of Dissolving Microneedles Loaded with the Water Extract of Diaphragma juglandis Fructus and Its Therapeutic Effect on Skin Ulcer in Mice

【目的】筛选分心木水提物微针的制备处方,同时考察其对小鼠皮肤溃疡模型的有效性。【方法】采用两步离心法制备分心木可溶性微针,对微针基质材料处方进行筛选,并测定不同浓度分心木水提物微针释药量,得到最佳基质处方,最终用于评价微针质量;采用化学灼烧法建立小鼠皮肤溃疡模型,模型小鼠随机分为生理盐水组、2%分心木水提物溶液涂布组、2%分心木水提物微针给药组和5%分心木水提物微针给药组,间隔3 d给药1次,期间对小鼠溃疡进行大体形态观察及面积测量,并对造模第14天时溃疡皮肤的羟脯氨酸含量进行检测,对溃疡皮肤组织块进行石蜡包埋切片,HE染色,光镜观察病理组织学变化。【结果】最终筛选得到5%透明质酸作为分心木水提物微针制备基质材料,且后续质量评价结果好;动物试验结果发现,与生理盐水组相比,给药组小鼠皮肤溃疡创面愈合率均显著提高,不同浓度微针组小鼠第14天时溃疡皮肤中羟脯氨酸含量显著增加,病理组织学检查结果表现出更好的愈合效果。【结论】试验制得的分心木水提物微针可有效促进小鼠皮肤溃疡创面愈合。

【Objective】This study aimed to screen the preparation formula of dissolving microneedles loaded with the water extract of Diaphragma juglandis Fructus and examine its effectiveness on mice skin ulcer model.【Method】A two-step centrifugation method was employed to prepare dissolving mi⁃croneedles.Initially,various microneedle matrix material formulations were screened,and the drug re⁃lease profiles of microneedles loaded with different concentrations of Diaphragma juglandis Fructus were evaluated to determine the optimal matrix composition,which was subsequently utilized to fabricate mi⁃croneedles.The skin ulcer mouse model was established by chemical burning method.The mice were ran⁃domly assigned to four groups,including normal saline group,2%Diaphragma juglandis Fructus water extract solution treating group,2%Diaphragma juglandis Fructus water extract dissolving microneedle treating group,and 5%Diaphragma juglandis Fructus water extract dissolving microneedle treating group.Treatments were administered once every three days.Throughout the experimental period,the pro⁃gression of skin ulcers was monitored,and the ulcer areas were measured accordingly.On the 14^(th)day af⁃ter modeling,the hydroxyproline content of the ulcerated skin in mice was determined.The tissue pieces of ulcer skin were paraffin-embedded and stained with HE,and the histopathological changes were ob⁃served under light microscope.【Result】Finally,5%hyaluronic acid was screened as the matrix mate⁃rial for the preparation of dissolving microneedles loaded with the water extract of Diaphragma juglandis Fructus,and the subsequent quality evaluation results were good.Compared to the normal saline group,the healing rates of skin ulcers were significantly enhanced in the treatment groups.Furthermore,the hy⁃droxyproline content in the ulcerated skin of mice showed a notable increase on the 14th day after mi⁃croneedle treatment.Histopathological examination via HE staining revealed superior healing of the ulcer⁃ated skin in mice treated with microneedles.【Conclusion】The microneedles prepared by this experi⁃ment can effectively promote the healing of skin ulcer wounds in mice.