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用于治疗角膜碱烧伤的具有抗炎和抗菌剂控释功能的双功能核壳电纺垫的研制。

Development of dual-functional core-shell electrospun mats with controlled release of anti-inflammatory and anti-bacterial agents for the treatment of corneal alkali burn injuries.

作者信息

Razavi Malihe Sadat, Ebrahimnejad Pedram, Javar Hamid Akbari, Weppelmann Thomas A, Akbari Jafar, Amoli Fahimeh Asadi, Atyabi Fatemeh, Dinarvand Rassoul

机构信息

Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran; Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Biomater Adv. 2023 Nov;154:213648. doi: 10.1016/j.bioadv.2023.213648. Epub 2023 Oct 2.

DOI:10.1016/j.bioadv.2023.213648
PMID:37812983
Abstract

In this study, a novel dual-drug carrier for the co-administration of an anti-inflammatory and antibiotic agent consisting of core-shell nanofibers for the treatment of cornea alkali burns was designed. The core-shell nanofibers were prepared via coaxial electrospinning of curcumin-loaded silk fibroin as the core and vancomycin-loaded chitosan/polyvinyl alcohol (PVA) as the shell. Electron microscopy (SEM and TEM) images confirmed the preparation of smooth, bead-free, and continuous fibers that formed clear core-shell structures. For further studies, nanofiber mats were cross-linked by heat treatment to avoid rapid disintegration in water and improve both mechanical properties and drug release. The release profile of curcumin and vancomycin indicated an initial burst release, continued by the extended release of both drugs within 72 hours. Rabbit corneal cells demonstrated high rates of proliferation when evaluated using a cell metabolism assay. Finally, the therapeutic efficiency of core/shell nanofibers in healing cornea alkali burn was studied by microscopic and macroscopic observation, fluorescence staining, and hematoxylin-eosin assay on rabbit eyes. The anti-inflammatory activity of fabricated fibers was evaluated by enzyme-linked immunosorbent assay and Immunofluorescence analysis. In conclusion, using a robust array of in vitro and in vivo experiments this study demonstrated the ability of the dual-drug carriers to promote corneal re-epithelialization, minimize inflammation, and inhibit corneal neovascularization. Since these parameters are critical to the healing of corneal wounds from alkali burns, we suggest that this discovery represents a promising future therapeutic agent that warrants further study in humans.

摘要

在本研究中,设计了一种新型双药载体,用于联合施用抗炎药和抗生素,其由核壳纳米纤维组成,用于治疗角膜碱烧伤。核壳纳米纤维通过同轴静电纺丝制备,以负载姜黄素的丝素蛋白为核,负载万古霉素的壳聚糖/聚乙烯醇(PVA)为壳。电子显微镜(SEM和TEM)图像证实制备出了光滑、无珠且连续的纤维,形成了清晰的核壳结构。为了进一步研究,通过热处理使纳米纤维垫交联,以避免在水中快速崩解,并改善机械性能和药物释放。姜黄素和万古霉素的释放曲线表明,最初有一个突释阶段,随后两种药物在72小时内持续缓释。使用细胞代谢测定法评估时,兔角膜细胞显示出高增殖率。最后,通过对兔眼进行显微镜和宏观观察、荧光染色以及苏木精-伊红测定,研究了核/壳纳米纤维在角膜碱烧伤愈合中的治疗效果。通过酶联免疫吸附测定和免疫荧光分析评估了所制备纤维的抗炎活性。总之,本研究通过一系列强大的体外和体内实验证明了双药载体促进角膜再上皮化、减轻炎症和抑制角膜新生血管形成的能力。由于这些参数对于碱烧伤角膜伤口的愈合至关重要,我们认为这一发现代表了一种有前途的未来治疗剂,值得在人体中进一步研究。

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