Nano‐Delivery of the Gramicidin Peptide for Enhancing Antimicrobial Activity

ANTEZANA, PABLO E.; MUNICOY, SOFIA; BELLINO, MARTÍN G.; MARTINI, FLORENCIA; DESIMONE, MARTÍN F.

EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY

WILEY-V C H VERLAG GMBH

Año: 2021

1438-7697

Gramicidin S (GraS) is an amphiphilic peptide that has emerged as an effective alternative antibiotic due to its distinctive mechanism of action trough disruption of the cell membrane of bacteria. However, its applicability as an antibiotic agent is restricted for clinical uses due to its effect on eukaryotic cells and low aqueous solubility. In this work, a novel water-soluble peptide formulation with bactericidal activity was developed by the incorporation of Gramicidin S in the lipid bilayer of liposomes (L-GraS). As a result, GraS included in the lipid vesicles was stabilized in aqueous medium and showed antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus). In addition, L-GraS revealed enhanced biocompatibility with mammalian cells in comparison with the free peptide treatment. These results were also analyzed using molecular dynamics (MD) simulations that shed light on the collective behavior between GraS peptides and liposomes from a molecular approach. The molecular dynamic simulations were in agreement with experimental results and further confirmed the effective incorporation of GraS in the liposomes, letting understand the best formulation procedure of the vesicles. Therefore, the liposomal GraS nanosystem presented here is an interesting alternative to conventional antibiotics, with less applicability restrictions and promising features to improve current therapies of bacterial wound infections.