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全反式维 A 酸和倍他米松双载柔性脂质体凝胶增强银屑病治疗效果。

Flexible liposomal gel dual-loaded with all-trans retinoic acid and betamethasone for enhanced therapeutic efficiency of psoriasis.

机构信息

Department of Pharmacy, The Third People's Hospital of Hangzhou, 38 West Lake Avenue, Hangzhou, 310009, China.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, China.

出版信息

J Nanobiotechnology. 2020 May 24;18(1):80. doi: 10.1186/s12951-020-00635-0.

Abstract

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.

摘要

背景

银屑病是一种慢性免疫介导的炎症性皮肤病,目前尚无有效治疗方法。全反式维 A 酸(TRA)和倍他米松(BT)的利用在治疗银屑病方面仍然面临困难,因为它们的稳定性相对较差,皮肤渗透性有限,且具有全身副作用。柔性脂质体在更深的皮肤渗透和减少药物副作用方面表现出色,有望有效治疗皮肤疾病。本工作旨在建立基于 TRA 和 BT 的双载柔性脂质体凝胶,以提高银屑病的治疗效果。

结果

本研究成功制备了 TRA 和 BT 共载的柔性脂质体。特征研究表明,柔性脂质体具有纳米级颗粒(约 70nm)、高药物包封效率(>98%)和持续的药物释放行为。与游离药物相比,柔性脂质体显著增加了药物的皮肤渗透和保留。HaCaT 细胞的结果表明,柔性脂质体无毒性,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最好的减轻表皮厚度和细胞因子(TNF-α和 IL-6)水平的能力,极大地缓解了银屑病的症状。

结论

TRA 和 BT 双载柔性脂质体发挥了协同作用,是一种有前途的治疗银屑病的局部治疗方法。

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