目的 制备聚乙二醇修饰的大黄素/大黄酸脂质体（PEGylated emodin/rhein-liposomes，PEG-Emo/Rhe-Lips）温敏凝胶，考察其对溃疡性结肠炎（ulcerative colitis，UC）模型小鼠的治疗作用。方法 薄膜水化法制备PEG-Emo/Rhe-Lips，采用Box-Behnken设计-效应面法（Box-Behnken design-response surface method，BBD-RSM）优化处方；透射电子显微镜（transmission electron microscope，TEM）观察PEG-Emo/Rhe-Lips微观形貌；将PEG-Emo/Rhe-Lips混悬液制备成温敏凝胶，考察其体外释药行为。建立小鼠UC模型，考察PEG-Emo/Rhe-Lips温敏凝胶对UC模型小鼠的治疗作用。结果 PEG-Emo/Rhe-Lips最佳处方：磷脂与胆固醇用量为10.4∶1，总脂质和总药物用量比为9.2∶1，磷脂与DSPE-mPEG₂₀₀₀用量比为3.9∶1。PEG-Emo/Rhe-Lips的包封率、载药量、粒径及ζ电位分别为（83.72±1.09）%、（7.51±0.12）%和（199.22±9.06）nm和（−17.64±0.58）mV，其形态近似球形。PEG-Emo/Rhe-Lips温敏凝胶表现出明显的缓释特征，大黄酸和大黄素在24 h累积释放率分别为88.16%和89.90%，释药机制均为扩散与溶蚀共同协调。药效学结果显示，PEG-Emo/Rhe-Lips温敏凝胶高剂量组（大黄素、大黄酸均为25 mg/kg）结肠长度、结肠湿质量、结肠指数和胸腺指数显著性增加（P＜0.05），疾病活动指数（disease activity index，DAI）、肠黏膜损伤评分和脾脏指数显著性下降（P＜0.05、0.01），其UC治疗效果更优。结论 PEG-Emo/Rhe-Lips温敏凝胶极大地提高了大黄素和大黄酸对UC的治疗作用，无明显刺激性，值得进一步开发。

Objective To prepare PEGylated emodin/rhein-liposomes (PEG-Emo/Rhe-Lips) thermosensitive gel, and to investigate its therapeutic effects on ulcerative colitis (UC) model mice.Methods PEG-Emo/Rhe-Lips was prepared by film hydration method. Box-Behnken design-response surface method (BBD-RSM) was used to optimize preparations of PEG-Emo/Rhe-Lips. Micromorphology of PEG-Emo/Rhe-Lips was observed by transmission electron microscopy (TEM). PEG-Emo/Rhe-Lips suspension was prepared into thermosensitive gel, drug release in vitro of PEG-Emo/Rhe-Lips thermosensitive gel was also studied. UC model was established, the therapeutic effects of PEG-Emo/Rhe-Lips on colitis was studied.Results Optimal formulations of PEG-Emo/Rhe-Lips: dosage ratio of phospholipids to cholesterol was 10.4:1, dosage ratio of total lipids was 9.2:1, dosage ratio of phospholipids to DSPE-mPEG₂₀₀₀ was 3.9:1. Encapsulation efficiency, drug loading, particle size and zeta potential of PEG-Emo/Rhe-Lips were (83.72 ± 1.09)%, (7.51 ± 0.12)%, (199.22 ± 9.06) nm and (−17.64 ± 0.58) mV, respectively. The morphology of PEG-Emo/Rhe-Lips was approximately spherical. PEG-Emo/Rhe-Lips thermosensitive gel exhibited obvious sustained-release characteristics, and the cumulative release rate of emodin and rhein were 88.16% and 89.90% in 24 h, respectively. Drug release mechanism was coexistence of diffusion and matrix erosion. Pharmacodynamics showed that the length of colon, colon wet weight, colon index and thymus index of PEG-Emo/Rhe-Lips temperature-sensitive gel were significantly increased (P < 0.05), the disease activity index (DAI), intestinal mucosal damage score and spleen index were significantly decreased (P < 0.05, 0.01), which showed that the UC therapeutic effects of PEG-Emo/Rhe-Lips temperature-sensitive gel was better.Conclusion PEG-Emo/Rhe-Lips temperature-sensitive gel greatly enhanced the therapeutic effects of emodin and rhein on colitis with no obvious irritation. Therefore, it was worth further developing.

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2024年省科技攻关项目（242102310456）；河南省高等学校重点科研项目（24B416004）；河南省医学教育研究项目（WJLX2023153）；山西省中央引导地方科技发展资金项目（YDZJSX2024B014）