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纳米封装贯叶连翘素与光动力疗法联合用于治疗皮肤癣菌病。

Nanoencapsulated hypericin in P-123 associated with photodynamic therapy for the treatment of dermatophytosis.

机构信息

Department of Analysis Clinics & Biomedicine, State University of Maringá, Paraná, Brazil.

Department of Physics, State University of Maringá, Paraná, Brazil.

出版信息

J Photochem Photobiol B. 2021 Feb;215:112103. doi: 10.1016/j.jphotobiol.2020.112103. Epub 2020 Dec 14.

DOI:10.1016/j.jphotobiol.2020.112103
PMID:33383558
Abstract

The antifungal application of photodynamic therapy (PDT) has been widely explored. According to superficial nature of tinea capitis and the facility of application of light sources, the use of nanoencapsulated hypericin in P-123 associated with PDT (P123-Hy-PDT) has been a poweful tool to treat this pathology. Thus, the aim of this study was to evaluate the efficiency of P123-Hy-PDT against planktonic cells and in a murine model of dermatophytosis caused by Microsporum canis. In vitro antifungal susceptibility and in vivo efficiency tests were performed, including a skin toxicity assay, analysis of clinical signs by evaluating score, and photoacoustic spectroscopy. In addition, tissue analyses by histopathology and levels of pro-inflammatory cytokines, such as quantitative and qualitative antifungal assays, were employed. The in vitro assays demonstrated antifungal susceptibility with 6.25 and 12.5 μmol/L P123-Hy-PDI; these experiments are the first that have used this treatment of animals. P123-Hyp-mediated PDT showed neither skin nor biochemical alteration in vivo; it was safe for dermatophytosis treatment. Additionally, the treatment revealed rapid improvement in clinical signs at the site of infection after only three treatment sessions, with a clinical score confirmed by photoacoustic spectroscopy. The mycological reduction occurred after six treatment sessions, with a statistically significant decrease compared with untreated infected animals. These findings showed that P123-Hy-PDT restored tissue damage caused by infection, a phenomenon confirmed by histopathological analysis and proinflammatory cytokine levels. Our results reveal for the first time that P123-Hy-PDT is a promising treatment for tinea capitis and tinea corporis caused by M. canis, because it showed rapid clinical improvement and mycological reduction without causing toxicity.

摘要

光动力疗法(PDT)的抗真菌应用已得到广泛探索。根据头癣的表浅性质和光源应用的便利性,纳米封装金丝桃素与 PDT(P123-Hy-PDT)联合应用已成为治疗这种疾病的有力工具。因此,本研究旨在评估 P123-Hy-PDT 对浮游细胞和犬小孢子菌引起的皮肤真菌病的小鼠模型的治疗效果。进行了体外抗真菌药敏试验和体内功效试验,包括皮肤毒性测定、评分评估临床症状以及光声光谱分析。此外,还进行了组织学分析和促炎细胞因子水平分析,包括定量和定性抗真菌测定。体外试验显示,P123-Hy-PDT 具有 6.25 和 12.5 μmol/L 的抗真菌敏感性;这是首次在动物中使用这种治疗方法。P123-Hyp 介导的 PDT 在体内既没有皮肤也没有生化改变,对皮肤真菌病的治疗是安全的。此外,该治疗方案在仅进行三次治疗后,感染部位的临床症状迅速改善,临床评分得到光声光谱的确认。经过六次治疗后,真菌数量减少,与未治疗的感染动物相比具有统计学意义。这些发现表明,P123-Hy-PDT 可恢复感染引起的组织损伤,组织学分析和促炎细胞因子水平证实了这一现象。我们的结果首次表明,P123-Hy-PDT 是治疗犬小孢子菌引起的头癣和体癣的一种很有前途的方法,因为它在不引起毒性的情况下表现出快速的临床改善和真菌学减少。

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