Delivery of antimicrobial peptides to model membranes by cubosome nanocarriers

Antimicrobial peptides (AMPs), which typically disrupt the bacterial wall prompting leakage or lysis of the cell, form a growing contingent in the arsenal against antibiotic resistant bacteria. The effectiveness of AMPs is, however, hampered by their low solubility, general chemical and physical instability, and short half-life in vivo. Lipid nanocarriers such as cubosomes are effective at encapsulating and protecting proteins while simultaneously showing promise in delivery applications. Here, the efficacy of cubosome mediated delivery of AMPs is evaluated by the in-situ surface characterization of model membranes with varying composition. The cubosomes were observed to initially fuse with the membranes, with subsequent membrane disruption observed after approximately 20 - 60 min. The time for the disruption was sensitive to the charge of the cubosome as well as the composition of the bilayer. More physiologically relevant bilayers including lipids with phospho-(10-rac-glycerol) (PG) or phosphoethanolamine (PE) headgroups were more vulnerable than those of neat phosphocholine (PC). Notably, disruption to the bilayer occurred an order of magnitude faster for encapsulated AMP compared to free AMP. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

Antimicrobial peptides (AMPs) are effective against antibiotic resistant bacteria, but their effectiveness is hindered by low solubility, instability, and short half-life. Lipid nanocarriers like cubosomes can encapsulate and protect AMPs while showing promise in delivery applications. Studies show that cubosome-mediated delivery of AMPs leads to faster membrane disruption, influenced by cubosome charge and bilayer composition.