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负载利巴韦林的电纺纳米纤维作为抗菌伤口敷料的制备与评价

Fabrication and evaluation of ribavirin-loaded electrospun nanofibers as an antimicrobial wound dressing.

作者信息

Alsulami Khulud A, Bakr Abrar A, Alshehri Abdullah A, Aodah Alhassan H, Almughem Fahad A, Alamer Ali A, Alharbi Lujain A, Alsuwayeh Deema S, Halwani Abdulrahman A, Alamoudi Abdullah A, Alfassam Haya A, Tawfik Essam A

机构信息

Advanced Diagnostics and Therapeutics Institute, Health Sector, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia.

Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Saudi Pharm J. 2024 May;32(5):102058. doi: 10.1016/j.jsps.2024.102058. Epub 2024 Apr 1.

Abstract

BACKGROUND

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.

RATIONALE

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

皮肤被视为抵御有害病原体的重要第一道防线,它承载着一个微生物生态系统,形成了种类繁多的皮肤微生物群。在慢性伤口中,宿主与微生物的相互作用发生改变,形成多微生物生物膜,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,尤其对金黄色葡萄球菌和铜绿假单胞菌有效,这两种菌是慢性伤口中已知的主要机会性病原体。

原理

在本研究中,开发了负载利巴韦林的电纺纳米纤维系统,作为一种潜在的伤口敷料用于慢性伤口的局部应用。本研究选择利巴韦林是因为抗菌(抗生素和抗真菌)耐药性的新出现情况以及发现新抗菌剂的尝试较少,这促使在对现有药物耐药的情况下重新利用现有药物作为替代解决方案。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失去武装,可能是预防耐药性的一个有前景的选择。环糊精(CD)被用于将利巴韦林配制成电纺纳米纤维递送系统,以增强利巴韦林的吸收并加速其局部使用时的释放。

结果

结果表明成功制备了利巴韦林纳米纤维,其纳米纤维表面没有珠子和孔隙。X射线衍射分析证实,利巴韦林经历了从结晶态到无定形态的物理转变。这种变化是由于电纺过程后的分子分散所致。此外,从载药结果观察到,CD提高了利巴韦林在纳米纤维中的包封效率。聚乙烯吡咯烷酮(PVP)和CD增加了释放到溶液中的利巴韦林以及纤维垫的崩解,随着负载利巴韦林的纤维开始从其边缘向中点分解,纤维垫收缩并最终溶解成凝胶状物质。评估了利巴韦林和CD对人皮肤成纤维细胞(HFF-1)的细胞毒性,结果显示在细胞暴露24小时后利巴韦林的安全性相对较高,而CD在24小时和48小时内是安全的。

结论

本研究为我们的纳米纤维系统在治疗慢性伤口方面的潜在应用提供了有价值的见解;然而,需要进一步的抗菌和其他研究来确认其安全性和有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db01/11004991/05e9533e9f7b/ga1.jpg

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