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含有抗病毒药物辅料的咽喉喷雾剂,作为 SARS-CoV-2 暴露后预防或治疗咽峡炎的有效早期策略。

Throat spray formulated with virucidal pharmaceutical excipients as an effective early prophylactic or treatment strategy against pharyngitis post-exposure to SARS-CoV-2.

机构信息

Department of Pharmaceutics, Egyptian Drug Authority Formerly Known as National Organization for Drug Control and Research (NODCAR), Giza, Egypt; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Sinai University, Kantara branch, Sinai 41636, Egypt.

Center of Excellence for Drug Preclinical Studies (CE-DPS), Pharmaceutical and Fermentation Industry Development Center, City of Scientific Research & Technological Applications, New Borg El Arab, Alexandria, Egypt.

出版信息

Eur J Pharm Biopharm. 2024 Jun;199:114279. doi: 10.1016/j.ejpb.2024.114279. Epub 2024 Apr 7.

Abstract

Our study aimed to develop a virucidal throat spray using bioactive compounds and excipients, focusing on the preparation of Curcumin (CUR) in a self-nano emulsifying drug delivery system (SNEDDS). Two molecular docking studies against SARS-CoV-2 targets guided the selection of proper oil, surfactant, co-surfactant, and natural bioactive that would maximize the antiviral activity of the throat spray. Two self-nanoemulsifying formulas that were diluted with different vehicles to prepare eight CUR-loaded SNESNS (self-nanoemulsifying self-nanosuspension) formulas. In vitro characterization studies and in vitro anti-SARS-CoV-2 effect revealed that the optimal formula, consisted of 20 % Anise oil, 70 % Tween 80, 10 % PEG 400, and 0.1 %w/w CUR, diluted with DEAE-Dx. Preclinical toxicity tests on male rats confirmed the safety of a mild throat spray dose (5 µg/mL CUR). In a rat model of acute pharyngitis induced by ammonia, post-treatment with the optimal formula of CUR loaded SNESNS for one week significantly reduced elevated proinflammatory markers (TNF-α, IL6, MCP1, and IL8). In conclusion, our CUR-loaded SNESNS formula, at 5 µg/mL concentration, shows promising effect as a prophylactic throat spray against SARS-CoV-2 and as a treatment for pharyngitis.

摘要

我们的研究旨在开发一种使用生物活性化合物和赋形剂的杀病毒喉咙喷雾剂,重点是在自纳米乳化药物传递系统(SNEDDS)中制备姜黄素(CUR)。两项针对 SARS-CoV-2 靶标的分子对接研究指导了适当油、表面活性剂、共表面活性剂和天然生物活性物质的选择,这些物质将最大限度地提高喉咙喷雾剂的抗病毒活性。两种自纳米乳化配方用不同的载体稀释,制备了 8 种负载 CUR 的 SNESNS(自纳米乳化自纳米混悬剂)配方。体外特性研究和体外抗 SARS-CoV-2 效果表明,最佳配方由 20%茴香油、70%吐温 80、10%PEG400 和 0.1%w/w CUR 组成,用 DEAE-Dx 稀释。雄性大鼠的临床前毒性试验证实了温和喉咙喷雾剂量(5µg/mL CUR)的安全性。在氨诱导的大鼠急性咽炎模型中,用负载 CUR 的 SNESNS 的最佳配方进行一周的后期治疗可显著降低升高的促炎标志物(TNF-α、IL6、MCP1 和 IL8)。总之,我们负载 CUR 的 SNESNS 配方在 5µg/mL 浓度下,作为 SARS-CoV-2 的预防性喉咙喷雾剂和咽炎治疗剂具有很大的潜力。

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