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采用脂质纳米粒实现甲氨蝶呤和依那西普的局部共递送:一种针对银屑病管理的靶向方法。

Topical co-delivery of methotrexate and etanercept using lipid nanoparticles: A targeted approach for psoriasis management.

机构信息

UCIBIO-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.

Serviço de Dermatologia do Centro Hospitalar e Universitário do Porto, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua D. Manuel II, s/n, 4099-001 Porto, Portugal.

出版信息

Colloids Surf B Biointerfaces. 2017 Nov 1;159:23-29. doi: 10.1016/j.colsurfb.2017.07.080. Epub 2017 Jul 29.

Abstract

Methotrexate is indicated in psoriasis systemic therapy and its topical administration may be an option to overcome several side effects. A targeted delivery may be achieved through etanercept. Thus, a combination targeted therapy using methotrexate and etanercept could bring new perspectives for psoriasis patients. This work intended to develop and characterize co-delivery of methotrexate and etanercept using lipid nanoparticles, mediated by a carbopol hydrogel and to evaluate their potential for delivering the drug into the skin with reduced transdermal permeation. The nanoparticles were physico-chemically characterized. In vitro methotrexate release from solid lipid nanoparticles revealed a sustained release for 8h. The solid lipid nanoparticles were non-toxic towards human keratinocytes and fibroblasts. Permeation studies using pig ear as model revealed enhanced skin deposition of the applied methotrexate when incorporated within solid lipid nanoparticles in relation to free drug. Therapeutic amounts of methotrexate were delivered to psoriatic human skin after application of solid lipid nanoparticles, with reduced transdermal permeation.

摘要

甲氨蝶呤适用于银屑病的系统治疗,其局部给药可能是克服多种副作用的一种选择。通过依那西普可以实现靶向递送。因此,使用甲氨蝶呤和依那西普的联合靶向治疗可能为银屑病患者带来新的视角。本工作旨在开发并表征使用脂质纳米粒共递送甲氨蝶呤和依那西普,通过卡波姆水凝胶介导,并评估其将药物递送至皮肤减少经皮渗透的潜力。纳米粒进行了物理化学表征。从固体脂质纳米粒中释放甲氨蝶呤的体外释放显示出 8 小时的持续释放。固体脂质纳米粒对人角质形成细胞和成纤维细胞没有毒性。使用猪耳作为模型的渗透研究表明,与游离药物相比,将甲氨蝶呤包封在固体脂质纳米粒中可增强应用药物在皮肤中的沉积。在应用固体脂质纳米粒后,治疗量的甲氨蝶呤被递送至银屑病人类皮肤,经皮渗透减少。

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