Researchers tested a tiny piece of the natural antimicrobial peptide LL‑37 (called LL17‑32) packaged inside tiny fat bubbles (liposomes) coated with chitosan to see if it could kill the gum‑disease bug P. gingivalis. The peptide stuck well to the bubbles but didn’t come out, so its killing power dropped compared to using the peptide on its own. The coating helped keep the bubbles stable, especially when the chitosan had a high degree of acetylation, hinting it could be used for slow‑release mouth products in the future.

Periodontal disease is triggered by surface bacterial biofilms where bacteria are less susceptible to antibiotic treatment. The development of liposome-based delivery mechanisms for the therapeutic use of antimicrobial peptides is an attractive alternative in this regard. The cationic antimicrobial peptide LL-37 (human cathelicidin) is well-known to exert antibacterial activity against <i>P</i> <i>orphyromonas</i> <i>gingivalis,</i> a keystone oral pathogen. However, the antibacterial activity of the 16-amino acid fragment (LL17-32) of LL-37, is unknown. In addition, there are still gaps in studies using liposomal formulations as delivery vehicles of antibacterial peptides against this pathogen. This study was designed to examine the influence of the different types of liposomal formulations to associate and deliver LL17-32 to act against <i>P. gingivalis</i>. Chitosans of varying Mw and degree of acetylation (DA) were adsorbed at the surface of soya lecithin (SL) liposomes. Their bulk (average hydrodynamic size, &#x3b6;-potential and membrane fluidity) and ultrastructural (<i>d</i>-spacing, half-bilayer thickness and the water layer thickness) biophysical properties were investigated by a panel of techniques (DLS, SAXS, M3-PALS, fluorescence spectroscopy and TEM imaging). Their association efficiency, <i>in vitro</i> release, stability, and efficacy in killing the periodontal pathogen <i>P. gingivalis</i> were also investigated. All liposomal systems possessed spherical morphologies and good shelf-life stabilities. Under physiological conditions, chitosan formulations with a high DA demonstrated enhanced stability in comparison to low DA-chitosan formulations. Chitosans and LL17-32 both decreased SL-liposomal membrane fluidity. LL17-32 exhibited a high degree of association with SL-liposomes without <i>in vitro</i> release. In biological studies, free LL17-32 or chitosans alone, demonstrated microbicidal activity against <i>P. gingivalis</i>, however this was attenuated when LL17-32 was loaded onto the SL-liposome delivery system, presumably due to the restrained release of the peptide. A property that could be harnessed in future studies (<i>e.g</i>., oral mucoadhesive slow-release formulations).