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载有地塞米松纳米颗粒的可溶解微针治疗眼部炎症的安全性和有效性

Safety and Efficacy of Dissolvable Microneedles Embedded with Dexamethasone-Loaded Nanoparticles for Treating Ocular Inflammation.

作者信息

Fitaihi Rawan, Alshamsan Aws, Abokhamees Shorooq, Raish Mohammad, Kalam Mohd Abul, Craig Duncan Q M

机构信息

Research Department of Pharmaceutics, School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia(1).

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia(1).

出版信息

Int J Pharm. 2025 Aug 20;681:125871. doi: 10.1016/j.ijpharm.2025.125871. Epub 2025 Jun 18.

Abstract

This study evaluates the ocular toxicity and therapeutic efficacy of a dissolvable microneedle (MN) system containing PLGA nanoparticles loaded with dexamethasone (Dex) using a rabbit model of endotoxin-induced uveitis. Previous research by our group demonstrated the potential of MN systems in delivering PLGA microparticles to scleral tissue. Building on this, we conducted an in-vivo study to assess the irritancy and therapeutic activity of Dex-loaded nanoparticles in MN patches. Results showed that both Blank-MN and Dex-MN patches caused minimal irritation, with no mechanical injury upon insertion. Dex-MN patches had a lower irritation score, and faster recovery compared to Blank-MN patches. In the uveitis model, Dex-MN patches significantly reduced clinical scores of uveitis and levels of pro-inflammatory markers (TNF-α, IL-6, MPO), and normalized apoptosis mediators (Bax, BCL2, NF-κB, Caspase3). Histopathological assessments confirmed reduced inflammatory reactions and cellular in-filtrate in Dex-MN treated eyes. These findings indicate that the Dex-loaded dissolvable MN system is a safe and effective platform for ocular drug delivery, offering significant therapeutic benefits in treating ocular inflammation.

摘要

本研究使用内毒素诱导的葡萄膜炎兔模型,评估了一种含有载有地塞米松(Dex)的聚乳酸-羟基乙酸共聚物(PLGA)纳米颗粒的可溶解微针(MN)系统的眼毒性和治疗效果。我们团队之前的研究证明了MN系统在将PLGA微粒递送至巩膜组织方面的潜力。在此基础上,我们进行了一项体内研究,以评估MN贴片中载有Dex的纳米颗粒的刺激性和治疗活性。结果显示,空白MN贴片和Dex-MN贴片均引起最小程度的刺激,插入时无机械损伤。与空白MN贴片相比,Dex-MN贴片的刺激评分更低,恢复更快。在葡萄膜炎模型中,Dex-MN贴片显著降低了葡萄膜炎的临床评分和促炎标志物(TNF-α、IL-6、MPO)的水平,并使凋亡介质(Bax、BCL2、NF-κB、Caspase3)恢复正常。组织病理学评估证实,Dex-MN治疗的眼睛炎症反应和细胞浸润减少。这些发现表明,载有Dex的可溶解MN系统是一种安全有效的眼部给药平台,在治疗眼部炎症方面具有显著的治疗益处。

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