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普林森-P123-光动力疗法在体外模型中作为治疗镰刀菌引起的甲真菌病的一种替代方法

Hypericin-P123-photodynamic therapy in an ex vivo model as an alternative treatment approach for onychomycosis caused by Fusarium spp.

机构信息

Department of Analysis Clinics and Biomedicine, State University of Maringa, Parana, Brazil.

Department of Chemistry, State University of Maringa, Parana, Brazil.

出版信息

Photodiagnosis Photodyn Ther. 2021 Sep;35:102414. doi: 10.1016/j.pdpdt.2021.102414. Epub 2021 Jun 26.

DOI:10.1016/j.pdpdt.2021.102414
PMID:34186264
Abstract

BackgroundFusarium has been considered an opportunistic pathogen, causing several infections in humans, including onychomycosis. In addition, a high resistance to conventional antifungals has been linked to this genus. Photodynamic Therapy (PDT), known as a non-invasive therapy, can be an alternative treatment for fungal infections, based on the excitation of a photosensitizing compound (PS) by a specific length of light, causing damage to the target. The aim of this study was to evaluate the effects of a formulation of Hypericin (Hyp) encapsulated in Pluronic™ (P123), via photodynamic therapy (PDT), on planktonic cells and biofilms in Fusarium spp. using in vitro and ex vivo assays. Materials & Methods epidemiology studies about Fusarium spp. in onychomycosis was perfomed, carried out molecular identification, compared the antifungal activity of the conventional antifungals with PDT with encapsulated Hypericin (Hyp-P123), carried out detection of reactive oxygen species, and measured the antibiofilm effect of the Hyp-P123-PDT in vitro and in an ex vivo model of onychomycosis. Results Hyp-P123-PDT exhibited a fungicidal effect in vitro with reductions ≥ 3 log. ROS generation increased post-Hyp-P123-PDT in Fusarium spp. Hyp-P123-PDT showed a potent inhibitory effect on adhesion-phase and mature biofilms in vitro tests and an ex vivo model of onychomycosis (p<0.0001). Conclusion Hyp-P123-PDT had a potent effect against Fusarium spp., suggesting that photodynamic therapy with Hyp-P123 is a safe and promising treatment for onychomycosis in clinical practice.

摘要

背景

镰刀菌被认为是一种机会性病原体,可导致人类多种感染,包括甲真菌病。此外,该属与对抗真菌药物的高度耐药性有关。光动力疗法(PDT),作为一种非侵入性治疗方法,可以作为治疗真菌感染的替代方法,其原理是通过特定波长的光激发光敏化合物(PS),从而对目标造成损害。本研究旨在通过体外和体内试验评估包裹在 Pluronic™(P123)中的金丝桃素(Hyp)制剂通过光动力疗法(PDT)对 Fusarium spp.浮游细胞和生物膜的影响。

材料和方法

对甲真菌病中 Fusarium spp.的流行病学研究进行了评估,进行了分子鉴定,比较了常规抗真菌药物与包裹金丝桃素(Hyp-P123)的 PDT 的抗真菌活性,进行了活性氧(ROS)检测,并测量了 Hyp-P123-PDT 在体外和体内甲真菌病模型中的抗生物膜作用。

结果

Hyp-P123-PDT 在体外具有杀菌作用,减少了≥3 对数。Hyp-P123-PDT 后 Fusarium spp.中的 ROS 生成增加。Hyp-P123-PDT 在体外试验和体内甲真菌病模型中对黏附期和成熟生物膜均显示出强大的抑制作用(p<0.0001)。

结论

Hyp-P123-PDT 对 Fusarium spp.具有强大的作用,表明 Hyp-P123 的光动力疗法是临床实践中治疗甲真菌病的一种安全且有前途的治疗方法。

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