目的 制备透皮肽修饰蛇床子素脂质体（transdermal peptide-modified osthole liposomes，TD-Ost-Lips），探究其经皮渗透性能和对特应性皮炎（atopic dermatitis，AD）的治疗作用。方法 薄膜分散法制备TD-Ost-Lips。选择磷脂与蛇床子素用量比、磷脂与胆固醇用量比、磷脂与二硬脂酰磷脂酰乙醇胺-聚乙二醇2000-透皮肽（DSPE-mPEG₂₀₀₀-TD）用量比作为TD-Ost-Lips主要影响因素，以包封率、载药量和粒径的总评归一值（overall desirability，OD）作为响应值，采用Box-Behnken设计-效应面法（Box-Behnken design-response surface method，BBD-RSM）优化TD-Ost-Lips处方。透射电子显微镜（transmission electron microscope，TEM）观察TD-Ost-Lips形貌。卡波姆940作为基质制备TD-Ost-Lips凝胶，透析法考察体外释药行为，探究释药机制，并考察流变学行为。Franz扩散池法考察TD-Ost-Lips凝胶经皮渗透性能。建立AD模型，观察各小鼠背部皮肤的皮损变化，并对炎症因子、皮损组织病理等进行检测。结果 TD-Ost-Lips最佳处方：磷脂与蛇床子素用量比为8.81∶1，磷脂与胆固醇用量比为6.27∶1，磷脂与DSPE-mPEG₂₀₀₀-TD用量比为4.72∶1。TD-Ost-Lips的平均包封率为（86.77±0.71）%，平均载药量为（6.65±0.10）%，平均粒径为（220.25±5.69）nm，ζ电位为（-17.31±0.85）mV，TD-Ost-Lips形貌呈囊泡状。TD-Ost-Lips凝胶24 h累积释放率为77.06%，释药行为符合Weibull模型。TD-Ost-Lips凝胶具有固体弹性性质，倒置后不流淌。TD-Ost-Lips凝胶将蛇床子素透皮速率、累积渗透量和皮肤滞留量分别提高至5.00、5.04、2.84倍。TD-Ost-Lips凝胶使皮损面积和严重程度（psoriasis area and severity index，PASI）明显下降，有效抑制了皮肤组织中炎症因子升高，并增强了蛇床子素对AD的治疗作用。结论 TD-Ost-Lips极大促进了蛇床子素的经皮渗透，显著增强了蛇床子素对AD的治疗作用，为进一步开发应用奠定基础。

Objective To prepare transdermal peptide-modified osthole liposomes (TD-Ost-Lips), and to explore the transdermal permeation performance and its therapeutic effects on atopic dermatitis (AD). Methods TD-Ost-Lips were prepared by film dispersion method. Phospholipid to osthole amount ratio, phospholipid to cholesterol amount ratio and phospholipid to DSPE-mPEG₂₀₀₀-TD amount ratio were selected as main influencing factors, overall desirability (OD) of entrapment efficiency, drug loading and particle size acted as response values, and the Box-Behnken design-response surface method (BBD-RSM) was used to optimize preparations of TD-Ost-Lips. Shape of TD-Ost-Lips was observed by transmission electron microscopy (TEM). TD-Ost-Lips gel was prepared using carbomer 940 as matrix, drug release behavior in vitro was studied by dialysis method and the mechanism of drug delivery was also studied. The rheology of TD-Ost-Lips gel was explored. The Franz diffusion cell method was used to study the transdermal permeation performance of TD-Ost-Lips gels. Atopic dermatitis (AD) model was stablished, the changes of skin lesions on the back of the mice were observed, and the inflammatory factors and pathological changes of skin lesions were detected. Results The optimal formulations of TD-Ost-Lips: phospholipid to osthole amount ratio was 8.81:1, phospholipid to cholesterol amount ratio was 6.27:1 and phospholipid to DSPE-mPEG2000-TD amount ratio was 6.27:1. The encapsulation efficiency, drug loading, particle size and ζ potential of TD-Ost-Lips were (86.77 ± 0.71)%, (6.65 ± 0.10)%, (220.25 ± 5.69) nm, and (−17.31 ± 0.85) mV, respectively. The shape of TD-Ost-Lips were vesicular. The cumulative release rate of TD-Ost-Lips gel in 24 h was 77.06%, and the drug behavior accorded with Weibull model. The rheological properties of TD-Ost-Lips gels showed solid elastic properties, and did not flow when inverted. TD-Ost-Lips gel increased the permeation rate, cumulative penetration and skin retention of osthole to 5.00, 5.04 and 2.84 times, respectively. TD-Ost-Lips gel significantly reduced the psoriasis area and severity index (PASI), effectively suppressed the elevation of inflammatory factors in skin tissue, and enhanced the treatment effect of osthole on AD. Conclusion TD-Ost-Lips gel greatly promoted the transdermal permeation of osthole, significantly enhanced its therapeutic effects on atopic dermatitis, and laid a foundation for further development and application.

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2026年度郑州市社科调研课题项目（ZSLX20261381）；2025年度河南省医学教育研究项目（WJLX2025238）；2025年度河南省医学教育研究项目（WJLX2025239）；2025年度河南应用技术职业学院校级科研项目（2025-SK-A66）；河南应用技术职业学院首席技师资助项目（2023-SXJS-HL02）