Skin is regarded as an essential first line of defense against harmful pathogens and it hosts an ecosystem of microorganisms that create a widely diverse skin microbiome. In chronic wounds, alterations in the host-microbe interactions occur forming polymicrobial biofilms that hinder the process of wound healing. Ribavirin, an antiviral drug, possesses antimicrobial activity, especially against and , which are known as the main opportunistic pathogens in chronic wounds. In this study, electrospun nanofiber systems loaded with ribavirin were developed as a potential wound dressing for topical application in chronic wounds. Ribavirin was chosen in this study owing to the emerging cases of antimicrobial (antibiotics and antifungal) resistance and the low attempts to discover new antimicrobial agents, which encouraged the repurposing use of current medication as an alternative solution in case of resistance to the available agents. Additionally, the unique mechanism of action of ribavirin, i.e., perturbing the bacterial virulence system without killing or stopping their growth and rendering the pathogens disarmed, might be a promising choice to prevent drug resistance. Cyclodextrin (CD) was utilized to formulate ribavirin as an electrospun nanofibers delivery system to enhance the absorption and accelerate the release of ribavirin for topical use. The results demonstrated a successful ribavirin nanofibers fabrication that lacked beads and pores on the nanofibrous surfaces. Ribavirin underwent a physical transformation from crystalline to amorphous form, as confirmed by X-ray diffraction analysis. This change occurred due to the molecular dispersion after the electrospinning process. Additionally, the CD enhanced the encapsulation efficiency of ribavirin in the nanofibers as observed from the drug-loading results. Polyvinylpyrrolidone (PVP) and CD increased ribavirin released into the solution and the disintegration of fibrous mats which shrank and eventually dissolved into a gel-like substance as the ribavirin-loaded fibers began to break down from their border toward the midpoint. Cytotoxicity of ribavirin and CD was evaluated against human dermal fibroblasts (HFF-1) and the results showed a relatively safe profile of ribavirin upon 24-hour cell exposure, while CD was safe within 24- and 48-hour. This study provides valuable insights into the potential application of our nanofibrous system for treating chronic wounds; however, further antimicrobial and studies are required to confirm its safety and effectiveness.

中文翻译：

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负载利巴韦林的静电纺纳米纤维作为抗菌伤口敷料的制备和评价

皮肤被认为是抵御有害病原体的重要第一道防线，它拥有一个微生物生态系统，可创造出广泛多样化的皮肤微生物组。在慢性伤口中，宿主-微生物相互作用发生改变，形成多种微生物生物膜，阻碍伤口愈合过程。利巴韦林是一种抗病毒药物，具有抗菌活性，特别是针对慢性伤口中主要的机会性病原体——细菌和细菌。在这项研究中，开发了负载利巴韦林的静电纺丝纳米纤维系统，作为局部应用于慢性伤口的潜在伤口敷料。本研究选择利巴韦林是因为抗菌药物（抗生素和抗真菌）耐药性病例不断出现，而且发现新抗菌药物的尝试较少，这鼓励重新利用现有药物作为现有药物耐药性的替代解决方案。此外，利巴韦林独特的作用机制，即扰乱细菌毒力系统而不杀死或阻止其生长并使病原体解除武装，可能是预防耐药性的一个有前途的选择。利用环糊精（CD）将利巴韦林配制为电纺纳米纤维递送系统，以增强利巴韦林的吸收并加速局部使用的释放。结果表明，利巴韦林纳米纤维的制造是成功的，纳米纤维表面上没有珠子和孔。 X 射线衍射分析证实，利巴韦林经历了从结晶形式到无定形形式的物理转变。这种变化是由于静电纺丝过程后分子分散而发生的。此外，从载药结果观察到，CD 提高了纳米纤维中利巴韦林的包封效率。聚乙烯吡咯烷酮 (PVP) 和 CD 增加了利巴韦林释放到溶液中以及纤维垫的崩解，当负载利巴韦林的纤维开始从其边界向中点分解时，纤维垫收缩并最终溶解成凝胶状物质。针对人真皮成纤维细胞 (HFF-1) 评估了利巴韦林和 CD 的细胞毒性，结果显示，利巴韦林在细胞暴露 24 小时后相对安全，而 CD 在 24 小时和 48 小时内是安全的。这项研究为我们的纳米纤维系统治疗慢性伤口的潜在应用提供了宝贵的见解；然而，需要进一步的抗菌和研究来确认其安全性和有效性。