BACKGROUND Psoriasis is a chronic immune-mediated inflammatory skin disease without effective treatment. The utilization of all trans-retinoic acid (TRA) and betamethasone (BT) for the treatment of psoriasis is still facing difficulties, due to their relatively poor stability, limited skin permeation, and systemic side effects. Flexible liposomes are excellent in deeper skin permeation and reducing the side effects of drugs, which is promising for effective treatment of skin disorders. This work aimed to establish dual-loaded flexible liposomal gel for enhanced therapeutic efficiency of psoriasis based on TRA and BT. RESULTS Flexible liposomes co-loaded with TRA and BT were successfully prepared in our study. The characterization examination revealed that flexible liposomes featured nano-sized particles (around 70 nm), high drug encapsulation efficiency (> 98%) and sustained drug release behaviors. Flexible liposomes remarkably increased the drug skin permeation and retention as compared with free drugs. Results on HaCaT cells suggested that flexible liposomes were nontoxic, and its cellular uptake has a time-dependent manner. In vivo studies suggested the topical application of TRA and BT dual-loaded liposomal gel had the best ability to reduce the thickness of epidermal and the level of cytokines (TNF-α and IL-6), largely alleviating the symptoms of psoriasis. CONCLUSIONS Flexible liposomal gel dual-loaded with TRA and BT exerted a synergistic effect, which is a promising topical therapeutic for the treatment of psoriasis.

中文翻译：

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双负载全反式视黄酸和倍他米松的柔性脂质体凝胶可提高牛皮癣的治疗效率。

背景技术牛皮癣是没有有效治疗的慢性免疫介导的炎性皮肤病。由于其相对较差的稳定性，有限的皮肤渗透性和全身性副作用，将所有反式维甲酸（TRA）和倍他米松（BT）用于牛皮癣的治疗仍然面临困难。柔性脂质体在深层皮肤渗透和减少药物副作用方面表现出色，这有望有效治疗皮肤疾病。这项工作旨在建立基于TRA和BT的双载柔性脂质体凝胶，以提高牛皮癣的治疗效率。结果在我们的研究中成功制备了与TRA和BT共同负载的柔性脂质体。表征检查显示，柔性脂质体具有纳米级颗粒（约70 nm），高的药物封装效率（> 98％）和持续的药物释放行为。与游离药物相比，柔性脂质体显着增加了药物皮肤的渗透和保留。HaCaT细胞的结果表明柔性脂质体是无毒的，其细胞摄取具有时间依赖性。体内研究表明，TRA和BT双载脂质体凝胶的局部应用具有减少表皮厚度和细胞因子（TNF-α和IL-6）水平的最佳能力，从而大大减轻了牛皮癣的症状。结论TRA和BT双重负载的柔性脂质体凝胶发挥协同作用，是治疗牛皮癣的有希望的局部治疗方法。与游离药物相比，柔性脂质体显着增加了药物皮肤的渗透和保留。HaCaT细胞的结果表明柔性脂质体是无毒的，其细胞摄取具有时间依赖性。体内研究表明，TRA和BT双载脂质体凝胶的局部应用具有减少表皮厚度和细胞因子（TNF-α和IL-6）水平的最佳能力，从而大大减轻了牛皮癣的症状。结论TRA和BT双重负载的柔性脂质体凝胶发挥协同作用，是治疗牛皮癣的有希望的局部治疗方法。与游离药物相比，柔性脂质体显着增加了药物皮肤的渗透和保留。HaCaT细胞的结果表明柔性脂质体是无毒的，其细胞摄取具有时间依赖性。体内研究表明，TRA和BT双载脂质体凝胶的局部应用具有减少表皮厚度和细胞因子（TNF-α和IL-6）水平的最佳能力，从而大大减轻了牛皮癣的症状。结论TRA和BT双重负载的柔性脂质体凝胶发挥协同作用，是治疗牛皮癣的有希望的局部治疗方法。体内研究表明，TRA和BT双载脂质体凝胶的局部应用具有减少表皮厚度和细胞因子（TNF-α和IL-6）水平的最佳能力，从而大大减轻了牛皮癣的症状。结论TRA和BT双重负载的柔性脂质体凝胶发挥协同作用，是治疗牛皮癣的有希望的局部治疗方法。体内研究表明，TRA和BT双载脂质体凝胶的局部应用具有减少表皮厚度和细胞因子（TNF-α和IL-6）水平的最佳能力，从而大大减轻了牛皮癣的症状。结论TRA和BT双重负载的柔性脂质体凝胶发挥协同作用，是治疗牛皮癣的有希望的局部治疗方法。