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两性霉素 B 速溶角膜内真菌感染微针贴片。

Rapidly dissolving microneedle patch of amphotericin B for intracorneal fungal infections.

机构信息

School of Pharmacy, Medical Biology Centre, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.

Biology Department, Science College, Basra University, Basra, Iraq.

出版信息

Drug Deliv Transl Res. 2022 Apr;12(4):931-943. doi: 10.1007/s13346-021-01032-2. Epub 2021 Jul 23.

Abstract

Chronic fungal infection of the cornea could lead to blindness if not treated properly. Topical amphotericin B (AMP-B) is considered the first treatment of choice for ocular fungal infection. However, factors related to its poor solubility and penetration through intact cornea lead to poor bioavailability. Microneedles (MNs) are emerging as a minimally invasive method to enhance ocular drug delivery. This study aims to investigate the potential use of biodegradable poly(vinylpyrrolidone) (PVP) and hyaluronic acid (HA)-based rapidly dissolving MNs for delivery of AMP-B to treat fungal infection. The data obtained illustrates PVP/HA MN arrays' reproducibility, good mechanical strength, and faster dissolution with 100% drug recovery. Multiphoton microscopic results revealed that MNs successfully penetrate the corneal tissue and enhance AMP-B permeation through corneal layers. Furthermore, PVP/HA MN arrays showed high solubility. Both PVP and HA successfully decreased AMP-B cytotoxicity when compared to free drug. More interestingly, the biocompatible MN formulations preserved the antifungal activity of AMP-B, as demonstrated by significant inhibition of fungal growth. Therefore, this study shows the feasibility of ocular delivery of the poorly soluble AMP-B using a fast-dissolving MN patch.

摘要

慢性真菌性角膜感染如果治疗不当可能导致失明。局部两性霉素 B(AMP-B)被认为是治疗眼部真菌感染的首选药物。然而,由于其溶解度差和完整角膜穿透性差,导致生物利用度低。微针(MN)作为一种微创方法,正逐渐成为增强眼部药物递送的方法。本研究旨在探讨可生物降解的聚乙烯吡咯烷酮(PVP)和透明质酸(HA)为基础的快速溶解 MN 用于递送 AMP-B 以治疗真菌感染的潜在用途。所得数据表明 PVP/HA MN 阵列具有可重复性、良好的机械强度和更快的溶解速度,药物回收率达到 100%。多光子显微镜结果显示 MN 成功穿透角膜组织,并增强 AMP-B 通过角膜层的渗透。此外,PVP/HA MN 阵列具有高溶解度。与游离药物相比,PVP 和 HA 均成功降低了 AMP-B 的细胞毒性。更有趣的是,生物相容的 MN 配方保留了 AMP-B 的抗真菌活性,真菌生长受到显著抑制。因此,本研究表明使用快速溶解的 MN 贴片进行眼部递送难溶性 AMP-B 的可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471f/8888497/b30fd3d91a0a/13346_2021_1032_Fig1_HTML.jpg

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