Cross-linked lyotropic liquid crystal particles functionalized with antimicrobial peptides

Antimicrobial peptides (AMPs) are promising alternatives to traditional antibiotics for addressing bacterial infections - including life-threatening antibiotic resistant infections. AMPs have a broad spectrum of antimicrobial activity and show a low probability to induce resistance. However, the poor serum stability of AMPs has limited their usage in clinical treatment. To enable improved serum stability while maintaining high antibacterial effect of AMPs, this study describes a material wherein AMPs are covalently bonded to micro-sized particles of cross-linked lyotropic liquid crystals, formed by the self-assembly of the block copolymer Pluronic F-127. The liquid crystal particles were shown to have antibacterial effect corresponding to a 4 log reduction against Staphylococcus aureus. The particles were structurally and chemically analyzed by small angle X-ray scattering, Fourier transform infra-red spectroscopy and Raman spectroscopy, confirming that the liquid crystal structure was maintained within the particles with the AMPs covalently bonded. The bonding to the particles gave the AMPs improved stability in serum, as they retained almost all of the antibacterial potency for 2 days compared to free AMPs, which lost all of its antibacterial potency within a day. Furthermore, insight regarding mode of action was obtained by cryogenic transmission electron microscopy, which showed the antimicrobial particles interacting with the surface of bacteria.

Automated summary

Antimicrobial peptides (AMPs) are potential alternatives to traditional antibiotics, with broad-spectrum antimicrobial activity and low probability of resistance. However, poor serum stability limits their clinical use. This study demonstrates a method to improve serum stability of AMPs by covalently bonding them to micro-sized particles of cross-linked lyotropic liquid crystals, while maintaining their antibacterial effect.