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一种负载大分子英夫利昔单抗的反相纳米胶束基透皮水凝胶:一种治疗类风湿性关节炎的创新方法。

A macromolecule infliximab loaded reverse nanomicelles-based transdermal hydrogel: An innovative approach against rheumatoid arthritis.

作者信息

Khan Dildar, Ahmed Naveed, Muhammad Adil, Shah Kifayat Ullah, Mir Maria, Rehman Asim Ur

机构信息

Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan.

Infection Medicine, College of Medicine and Veterinary Medicine, the University of Edinburgh, EH16 4UU, United Kingdom.

出版信息

Biomater Adv. 2025 Feb;167:214093. doi: 10.1016/j.bioadv.2024.214093. Epub 2024 Oct 30.

DOI:10.1016/j.bioadv.2024.214093
PMID:39492133
Abstract

Infliximab (IFX) is used as a biotherapeutic agent for the treatment of rheumatoid arthritis (RA); however, its biological activity is lost orally because of variations in gastric pH and enzymatic degradation, and reduced bioavailability. The authors have tried to improve the efficacy of macromolecule delivery through transdermal route. Polycaprolactone-Polyethylene glycol-Polycaprolactone (PCL-PEG-PCL) triblock copolymer previously synthesized and was used as an efficient carrier for the preparation of IFX loaded reverse nanomicelles (IFX-RNMs). The RNMs were fabricated via nanoprecipitation technique, characterized and then were incorporated into a Carbopol-based hydrogel with eucalyptus oil (EO) as a penetration enhancer. The optimized RNMs had a particle size of 72.32 nm and an encapsulation efficiency of 83 %. In vitro release, exhibited a sustained pattern of IFX from the prepared carrier system, ex-vivo skin permeation and fluorescence microscopic studies revealed that IFX-RNMs loaded hydrogel with EO markedly improved permeation. An in vivo study was carried out on a CFA-induced RA mice model that revealed significant improvements in the results of behavioral parameters, biochemical assays, histopathological and radiological analysis. Overall, the results concluded that the IFX-RNMs loaded hydrogel can be used as a suitable approach for treating RA.

摘要

英夫利昔单抗(IFX)用作治疗类风湿性关节炎(RA)的生物治疗剂;然而,由于胃内pH值变化和酶降解,其生物活性口服时丧失,生物利用度降低。作者试图通过经皮途径提高大分子递送的疗效。先前合成的聚己内酯-聚乙二醇-聚己内酯(PCL-PEG-PCL)三嵌段共聚物用作制备负载IFX的反向纳米胶束(IFX-RNMs)的有效载体。通过纳米沉淀技术制备RNMs,进行表征,然后将其掺入以卡波姆为基础的水凝胶中,并加入桉叶油(EO)作为渗透促进剂。优化后的RNMs粒径为72.32nm,包封率为83%。体外释放显示IFX从制备的载体系统中呈持续释放模式,离体皮肤渗透和荧光显微镜研究表明,负载IFX-RNMs的含EO水凝胶显著改善了渗透。在CFA诱导的RA小鼠模型上进行了体内研究,结果显示行为参数、生化分析、组织病理学和放射学分析结果有显著改善。总体而言,结果表明负载IFX-RNMs的水凝胶可作为治疗RA的合适方法。

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