Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland.
Pharmaceutical Laboratory Avena Sp.z.o.o., 86-031 Osielsko, Poland.
Int J Mol Sci. 2019 Jan 17;20(2):393. doi: 10.3390/ijms20020393.
The widespread use of biomaterials such as contact lenses is associated with the development of biofilm-related infections which are very difficult to manage with standard therapies. The formation of bacterial biofilms on the surface of biomaterials is associated with increased antibiotic resistance. Owing to their promising antimicrobial potential, lipopeptides are being intensively investigated as novel antimicrobials. However, due to the relatively high toxicity exhibited by numerous compounds, a lot of attention is being paid to designing new lipopeptides with optimal biological activities. The principal aim of this study was to evaluate the potential ophthalmic application of lipopeptide (C)₂-KKKK-NH₂. This lipopeptide was synthesized according to Fmoc chemistry using the solid-phase method. The antibiofilm activities of the lipopeptide, antibiotics used in ocular infections, and commercially available lens liquids were determined using the broth dilution method on polystyrene 96-well plates and contact lenses. Resazurin was applied as the cell-viability reagent. The effectiveness of the commercially available lens liquids supplemented with the lipopeptide was evaluated using the same method and materials. (C)₂-KKKK-NH₂ exhibited stronger anti-biofilm properties compared to those of the tested conventional antimicrobials and showed the ability to enhance the activity of lens liquids at relatively low concentrations (4⁻32 mg/L). Estimation of the eye irritation potential of the lipopeptide using Toxtree software 2.6.13 suggests that the compound could be safely applied on the human eye. The results of performed experiments encourage further studies on (C)₂-KKKK-NH₂ and its potential application in the prophylaxis of contact lens-related eye infections.
生物材料(如隐形眼镜)的广泛应用与生物膜相关感染的发展有关,这些感染用标准疗法很难治疗。生物材料表面上细菌生物膜的形成与抗生素耐药性增加有关。由于其具有有前景的抗菌潜力,脂肽被作为新型抗菌药物进行了深入研究。然而,由于许多化合物表现出相对较高的毒性,因此人们非常关注设计具有最佳生物学活性的新型脂肽。本研究的主要目的是评估脂肽(C)₂-KKKK-NH₂在眼部应用的潜力。该脂肽是根据 Fmoc 化学原理,通过固相法合成的。使用肉汤稀释法在聚苯乙烯 96 孔板和隐形眼镜上,确定了脂肽、用于眼部感染的抗生素和市售隐形眼镜护理液的抗生物膜活性。使用 Resazurin 作为细胞活力试剂。使用相同的方法和材料评估了市售隐形眼镜护理液中添加脂肽的效果。(C)₂-KKKK-NH₂的抗生物膜性能强于测试的常规抗生素,并且在相对较低的浓度(4⁻32 mg/L)下显示出增强隐形眼镜护理液活性的能力。使用 Toxtree 软件 2.6.13 估计脂肽的眼部刺激性潜力表明,该化合物可安全应用于人眼。进行的实验结果鼓励进一步研究(C)₂-KKKK-NH₂及其在预防隐形眼镜相关眼部感染中的潜在应用。