Instituto de Ciencia y Tecnología de Polímeros (ICTP-CSIC), C/Juan de la Cierva 3, Madrid 28006, Spain.
Universidad Nacional de Educación a Distancia (UNED), C/Bravo Murillo 38, Madrid 28015, Spain.
ACS Appl Bio Mater. 2023 Nov 20;6(11):4805-4813. doi: 10.1021/acsabm.3c00576. Epub 2023 Oct 20.
Combining different antimicrobial agents has emerged as a promising strategy to enhance efficacy and address resistance evolution. In this study, we investigated the synergistic antimicrobial effect of a cationic biobased polymer and the antimicrobial peptide (AMP) temporin L, with the goal of developing multifunctional electrospun fibers for potential biomedical applications, particularly in wound dressing. A clickable polymer with pendent alkyne groups was synthesized by using a biobased itaconic acid building block. Subsequently, the polymer was functionalized through click chemistry with thiazolium groups derived from vitamin B1 (PTTIQ), as well as a combination of thiazolium and AMP temporin L, resulting in a conjugate polymer-peptide (PTTIQ-AMP). The individual and combined effects of the cationic PTTIQ, Temporin L, and PTTIQ-AMP were evaluated against Gram-positive and Gram-negative bacteria as well as Candida species. The results demonstrated that most combinations exhibited an indifferent effect, whereas the covalently conjugated PTTIQ-AMP displayed an antagonistic effect, potentially attributed to the aggregation process. Both antimicrobial compounds, PTTIQ and temporin L, were incorporated into poly(lactic acid) electrospun fibers using the supercritical solvent impregnation method. This approach yielded fibers with improved antibacterial performance, as a result of the potent activity exerted by the AMP and the nonleaching nature of the cationic polymer, thereby enhancing long-term effectiveness.
将不同的抗菌剂结合使用已成为一种增强疗效和应对耐药性进化的有前途的策略。在这项研究中,我们研究了阳离子生物基聚合物和抗菌肽(AMP)temporin L 的协同抗菌作用,旨在开发多功能电纺纤维,用于潜在的生物医学应用,特别是在伤口敷料方面。使用生物基衣康酸构建块合成了带有炔基侧基的可点击聚合物。随后,通过点击化学将聚合物官能化,得到了源自维生素 B1 的噻唑基团(PTTIQ)以及噻唑和 AMP temporin L 的组合,得到了共轭聚合物-肽(PTTIQ-AMP)。单独和组合使用阳离子 PTTIQ、Temporin L 和 PTTIQ-AMP 对革兰氏阳性和革兰氏阴性细菌以及念珠菌属进行了评估。结果表明,大多数组合表现出无差异的作用,而共价共轭的 PTTIQ-AMP 则表现出拮抗作用,这可能归因于聚集过程。将抗菌化合物 PTTIQ 和 temporin L 都通过超临界溶剂浸渍法掺入聚乳酸电纺纤维中。这种方法提高了纤维的抗菌性能,这是由于 AMP 的强大活性和阳离子聚合物的非浸出性质,从而增强了长期效果。