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比较深共晶溶剂和环糊精配合物作为姜黄素载体用于蓝光光动力抗菌疗法。

Comparing deep eutectic solvents and cyclodextrin complexes as curcumin vehicles for blue-light antimicrobial photodynamic therapy approaches.

机构信息

3B's Research Group, I3Bs-Research Institute on Biomaterials, Biodegradables and Biomimetics, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Avepark, Zona Industrial da Gandra, 4805-017, Barco GMR, Portugal.

ICVS/3B's PT Government Associated Laboratory, Braga, Guimarães, Portugal.

出版信息

Photochem Photobiol Sci. 2022 Jul;21(7):1159-1173. doi: 10.1007/s43630-022-00197-0. Epub 2022 Apr 2.

Abstract

Curcumin (Cur), a polyphenolic compound derived from Curcuma longa L., has garnered the attention of the scientific community due to its remarkable biological properties such as its potential as a photosensitizing agent for photodynamic therapy (PDT). However, due to its low solubility in aqueous media and instability at physiological and alkaline pH, Cur has struggled to find relevant clinical application. To tackle these shortcomings, two distinct Cur-based formulations based on either complexation with methyl-β-cyclodextrin (MβCD), MβCDC-Cur, or dissolution in a choline chloride (ChCl): glycerol (Gly) deep eutectic solvent (DES), DES-Cur, were produced, physio-chemically characterized and compared regarding their potential as phototherapeutic agents for blue-light antimicrobial photodynamic therapy (aPDT) approaches. Both MβCD-Cur and DES-Cur were able to greatly enhance Cur solubility profile when compared to Cur powder. However, MβCD-Cur appears to hinder some of Cur's basal biological properties and possessed greater basal cytotoxicity towards L929 murine fibroblast cell line. Furthermore, MβCD-Cur was less photo-responsive when exposed to light which may hamper its application in blue-light aPDT approaches. In contrast, DES-Cur showed good biological properties and high photoresponsivity, displaying relevant phototoxicity against bacterial pathogens (≥ 99.9% bacterial reduction) while being better tolerated by L929 murine cells. Overall, this study found DES to be the more effective vehicle for Cur in terms of phototherapeutic potential which will serve as basis to develop novel platforms and approaches for blue-light aPDT targeting localized superficial infections.

摘要

姜黄素(Cur)是一种源自姜黄(Curcuma longa L.)的多酚化合物,由于其具有作为光动力疗法(PDT)光敏剂的潜在用途等显著的生物学特性,引起了科学界的关注。然而,由于其在水介质中的低溶解度和在生理和碱性 pH 下的不稳定性,Cur 难以找到相关的临床应用。为了解决这些缺点,制备了两种基于姜黄素的不同制剂,一种是与甲基-β-环糊精(MβCD)复合的制剂(MβCDC-Cur),另一种是溶解在胆碱氯化物(ChCl):甘油(Gly)深共晶溶剂(DES)中的制剂(DES-Cur),对其理化性质进行了表征,并比较了它们作为蓝光抗菌光动力疗法(aPDT)方法的光疗剂的潜力。与 Cur 粉末相比,MβCD-Cur 和 DES-Cur 均能显著提高 Cur 的溶解度。然而,MβCD-Cur 似乎会阻碍 Cur 的一些基础生物学特性,并对 L929 鼠成纤维细胞系表现出更大的基础细胞毒性。此外,与 DES-Cur 相比,MβCD-Cur 在暴露于光线下时的光反应性较差,这可能会阻碍其在蓝光 aPDT 方法中的应用。相比之下,DES-Cur 表现出良好的生物学特性和高光反应性,对细菌病原体显示出相关的光毒性(≥99.9%细菌减少),同时对 L929 鼠细胞的耐受性更好。总的来说,本研究发现 DES 是 Cur 在光疗潜力方面更有效的载体,这将为开发针对局部浅表感染的新型蓝光 aPDT 平台和方法提供基础。

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