目的 制備雙氫青蒿素脂質(zhì)體（DHA-LPs），并評(píng)價(jià)其外用治療銀屑病的作用。方法 采用薄膜分散法制備DHALPs，利用單因素試驗(yàn)結(jié)合Box-Behnken設(shè)計(jì)-響應(yīng)面法（BBD-RSM）優(yōu)化工藝參數(shù)，采用透射電子顯微鏡（TEM）、動(dòng)態(tài)透析法及穩(wěn)定性考察評(píng)價(jià)其理化性質(zhì)。采用咪喹莫特（IMQ）誘導(dǎo)的小鼠銀屑病樣皮損模型，結(jié)合HE染色、血常規(guī)分析、ELISA分析評(píng)價(jià)DHA-LPs的抗銀屑病作用。結(jié)果 DHA-LPs確定的最佳制備工藝為：二氯甲烷為溶劑、藥脂比1∶4.329、膽固醇與磷脂比1∶1.833、水化溫度46℃。測(cè)得DHA-LPs粒徑（97.39±0.50）nm、多分散系數(shù)（0.275±0.002）、ζ電位（-14.52±0.08）mV、包封率（76.03±0.47）%，載藥量（31.21±1.53）%。TEM顯示DHA-LPs呈橢球形，體外釋放呈雙相模式，4℃儲(chǔ)存28 d穩(wěn)定性良好。動(dòng)物藥效學(xué)結(jié)果顯示，與DHA溶液相比，DHA-LPs顯著緩解IMQ誘導(dǎo)的小鼠銀屑病樣皮損，逆轉(zhuǎn)IMQ誘導(dǎo)的小鼠脾臟系數(shù)升高，改善IMQ誘導(dǎo)的表皮結(jié)構(gòu)、脾臟結(jié)構(gòu)及中性粒細(xì)胞和單核細(xì)胞的異常，降低血清中促炎因子［白細(xì)胞介素（IL）-6、IL-17、IL-23、腫瘤壞死因子-α（TNF-α）］水平，升高小鼠血清中抑炎因子［轉(zhuǎn)化生長因子-β（TGF-β）］水平。結(jié)論 雙氫青蒿素外用緩解小鼠銀屑病樣皮損，將其制備成脂質(zhì)體制劑能夠增強(qiáng)其抗銀屑病作用，拓展了青蒿素類藥物的應(yīng)用范疇，為銀屑病的治療提供了一種新的策略。

Objective To prepare dihydroartemisinin liposomes (DHA-LPs) and evaluate their efficacy in the treatment of psoriasis when applied topically.Methods DHA-LPs were prepared using the thin film dispersion method. The process parameters were optimized by single-factor experiments combined with Box-Behnken design-response surface methodology (BBD-RSM). The physicochemical properties of DHA-LPs were evaluated by transmission electron microscopy (TEM), dynamic dialysis, and stability studies. The antipsoriasis effect of DHA-LPs was evaluated using an imiquimod (IMQ)-induced psoriasis-like skin lesion model in mice, combined with HE staining, blood routine analysis, and ELISA analysis.Results The optimal preparation process of DHA-LPs was determined as follows: dichloromethane as the solvent, drug-to-lipid ratio of 1∶4.329, cholesterol-to-phospholipid ratio of 1∶1.833, and hydration temperature of 46 ℃. The particle size of DHA-LPs was (97.39 ± 0.50) nm, the polydispersity index was (0.275 ± 0.002), the ζ potential was (-14.52 ± 0.08) mV, the entrapment efficiency was (76.03 ± 0.47)%, and the drug loading was (31.21 ± 1.53)%. TEM showed that DHA-LPs were ellipsoidal in shape, and the in vitro release followed a biphasic pattern. The stability of DHA-LPs was good after 28 days of storage at 4 ℃. The animal pharmacodynamics results showed that compared with DHA solution, DHA-LPs significantly alleviated IMQ-induced psoriasis-like skin lesions in mice, reversed the increase in spleen coefficient induced by IMQ, improved the abnormal epidermal and splenic structures and neutrophile granulocytes and monocytes induced by IMQ, and reduced the levels of pro-inflammatory factors [(Interleukin (IL)-6, IL-17, IL-23, Tumor necrosis factor-α (TNF-α)] in serum while increasing the level of anti-inflammatory factor [Transforming growth factor-β (TGF-β)] in mouse serum.Conclusion Topical application of dihydroartemisinin can alleviate psoriasis-like skin lesions in mice. Preparing it into liposomal formulation can enhance its antipsoriasis effect, expanding the application scope of artemisinin derivatives and providing a new strategy for the treatment of psoriasis.

R283.6

國家自然科學(xué)基金資助項(xiàng)目（82173767）；山西省基礎(chǔ)研究計(jì)劃（自由探索類）青年科學(xué)研究項(xiàng)目（202403021212250）；山西省博士啟動(dòng)基金資助項(xiàng)目（SD2420）；山西醫(yī)科大學(xué)校級(jí)博士啟動(dòng)基金資助項(xiàng)目（XD2313）