Silver compounds are widely known for their antimicrobial activity, but can exert toxic effects to the host. Among the strategies to reduce its toxicity, incorporation into biopolymers has shown promising results. We investigated the green syntheses of silver nanoparticles (AgNPs) and their functionalization in a chitosan matrix (AgNPs@Chi) as a potential treatment against Candida spp. Inhibitory concentrations ranging between 0.06 and 1 μg/ml were observed against distinct Candida species. Nanocomposite-treated cells displayed cytoplasmic degeneration and a cell membrane and wall disruption. Silver nanocomposites in combination with fluconazole and amphotericin B showed an additive effect when analyzed by the Bliss method. The low cytotoxicity displayed in mammalian cells and in the Galleria mellonella larvae suggested their potential use in vivo. When tested as a topical treatment against murine cutaneous candidiasis, silver nanocomposites reduced the skin fungal burden in a dose-response behavior and favored tissue repair. In addition, the anti-biofilm effect of AgNPs@Chi in human nail model was demonstrated, suggesting that the polymeric formulation of AgNPs does not affect antifungal activity even against sessile cells. Our results suggest that AgNPs@Chi seems to be a less toxic and effective topical treatment for superficial candidiasis. Lay Summary This study demonstrated the efficacy of silver nanoparticles (AgNPs) in inhibiting the growth of Candida. AgNPs incorporated in chitosan displayed a reduced toxicity. Tests in infected mice showed the effectiveness of the treatment. AgNPs-chitosan could be an alternative to combat candidiasis.

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银壳聚糖纳米复合材料作为浅表念珠菌病的潜在治疗方法

银化合物因其抗菌活性而广为人知，但会对宿主产生毒性作用。在降低其毒性的策略中，将其掺入生物聚合物中已显示出有希望的结果。我们研究了银纳米粒子 (AgNPs) 的绿色合成及其在壳聚糖基质 (AgNPs@Chi) 中的功能化，作为针对念珠菌属的潜在治疗方法。观察到针对不同念珠菌的抑制浓度范围在 0.06 和 1 μg/ml 之间。纳米复合材料处理的细胞表现出细胞质变性和细胞膜和细胞壁破坏。当通过 Bliss 方法分析时，银纳米复合材料与氟康唑和两性霉素 B 组合显示出累加效应。在哺乳动物细胞和大孔菌幼虫中表现出的低细胞毒性表明它们在体内的潜在用途。当作为针对小鼠皮肤念珠菌病的局部治疗进行测试时，银纳米复合材料在剂量反应行为中减少了皮肤真菌负担并有利于组织修复。此外，AgNPs@Chi 在人类指甲模型中的抗生物膜作用得到了证实，这表明 AgNPs 的聚合物制剂即使对固着细胞也不影响抗真菌活性。我们的结果表明，AgNPs@Chi 似乎是一种毒性较小且有效的浅表念珠菌病局部治疗。总结 本研究证明了银纳米粒子 (AgNPs) 在抑制念珠菌生长方面的功效。加入壳聚糖中的 AgNPs 显示出降低的毒性。对受感染小鼠的测试显示了治疗的有效性。AgNPs-壳聚糖可能是对抗念珠菌病的替代品。