1. Cubosome lipid nanocarriers for delivery of ultra-short antimicrobial peptides.
- Author
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Lakic B, Beh C, Sarkar S, Yap SL, Cardoso P, Valery C, Hung A, Jones NC, Hoffmann SV, Blanch EW, Dyett B, and Conn CE
- Subjects
- Microbial Sensitivity Tests, Molecular Dynamics Simulation, Antimicrobial Cationic Peptides chemistry, Antimicrobial Cationic Peptides pharmacology, Methicillin-Resistant Staphylococcus aureus drug effects, Lipids chemistry, Antimicrobial Peptides chemistry, Antimicrobial Peptides pharmacology, Particle Size, Drug Carriers chemistry, Escherichia coli drug effects, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents administration & dosage, Nanoparticles chemistry
- Abstract
Hypothesis: Although antimicrobial peptides (AMPs) are a promising class of new antibiotics, their inherent susceptibility to degradation requires nanocarrier-mediated delivery. While cubosome nanocarriers have been extensively studied for delivery of AMPs, we do not currently understand why cubosome encapsulation improves antimicrobial efficacy for some compounds but not others. This study therefore aims to investigate the link between the mechanism of action and permeation efficiency of the peptides, their encapsulation efficacy, and the antimicrobial activity of these systems., Experiments: Encapsulation and delivery of Indolicidin, and its ultra-short derivative, Priscilicidin, were investigated using SAXS, cryo-TEM and circular dichroism. Molecular dynamics simulations were used to understand the loading of these peptides within cubosomes. The antimicrobial efficacy was assessed against gram-negative (E. coli) and gram-positive (MRSA) bacteria., Findings: A high ionic strength solution was required to facilitate high loading of the cationic AMPs, with bilayer encapsulation driven by tryptophan and Fmoc moieties. Cubosome encapsulation did not improve the antimicrobial efficacy of the AMPs consistent with their high permeation, as explained by a recent 'diffusion to capture model'. This suggests that cubosome encapsulation may not be an effective strategy for all antimicrobial compounds, paving the way for improved selection of nanocarriers for AMPs, and other antimicrobial compounds., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Biserka Lakic reports financial support was provided by European Union. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2025
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