Pathogenic bacteria use quorum sensing (QS), a cell-to-cell communication process that uses small signalling molecules, to regulate several essential virulence factors such as bioluminescence, biofilm formation, and bacterial motility. Naringenin, a bitter and colourless flavanone ubiquitous in herbs and fruits, has been shown to inhibit QS activity in P. aeruginosa by decreasing the production of pyocyanin and elastase. In this study, to evaluate the anti-QS activity of naringenin against an E. coli Top 10 biosensor, we developed a novel system using sulfobutyl ether β-cyclodextrin (Captisol®) surface-adsorbed nanoformulations loaded with naringenin. The results showed that in both the nanocapsule (NC) and nanoemulsion (NE) formulations, the obtained colloidal particles have an appropriate size distribution and high association efficiency of naringenin, namely ~ 92.88 and ~ 67.98%, respectively. These formulations remained stable for 24 h and showed a biphasic controlled release profile in bacterial M9 medium. Captisol® was effectively immobilized on the NC’s surface, resulting in a surface charge inversion from positive (~ + 42 mV) to negative (~ -32mV). The biosensor assay revealed that NC outperformed NE in quenching the QS response and the incorporation of naringenin at the NC’s multifunctional surface enhanced this bioactivity. Cytotoxicity assays showed that when it was associated in NC, naringenin at a concentration of 188 μM was not cytotoxic to Caco2 cells, thus highlighting the cytoprotective effect of the developed formulation. Biofilm formation, a QS-mediated virulence factor, was inhibited up to ~ 60% in naringenin-loaded NC (188 μM), indicating the synergistic effect of positively charged chitosan with the bioactivity of naringenin and the NC’ advantageous high surface area-to-volume ratio.
Hao Thanh Nguyen, Andreas Hensel, Francisco M. Goycoolea (2021) Chitosan/cyclodextrin surface-adsorbed naringenin-loaded nanocapsules enhance bacterial quorum quenching and anti-biofilm activities. Colloids and Surfaces B: Biointerfaces 112281, https://doi.org/10.1016/j.colsurfb.2021.112281.