Chitosan/Cyclodextrin/TPP Nanoparticles Loaded with Quercetin as Novel Bacterial Quorum Sensing Inhibitors

The widespread emergence of antibiotic-resistant bacteria has highlighted the urgent need of alternative therapeutic approaches for human and animal health. Targeting virulence factors that are controlled by bacterial quorum sensing (QS), seems a promising approach. The aims of this study were to generate novel nanoparticles (NPs) composed of chitosan (CS), sulfo-butyl-ether-β-cyclodextrin (Captisol^®) and/or pentasodium tripolyphosphate using ionotropic gelation technique, and to evaluate their potential capacity to arrest QS in bacteria. The resulting NPs were in the size range of 250-400 nm with CS_70/5 and 330-600 nm with CS_70/20, had low polydispersity index (<0.25) and highly positive zeta potential ranging from ζ ~+31 to +40 mV. Quercetin, a hydrophobic model flavonoid, could be incorporated proportionally with increasing amounts of Captisol^® in the NPs formualtion, without altering significantly its physicochemical properties. Elemental analysis and FTIR studies revealed that Captisol^® and quercetin were effectively integrated into the NPs. These NPs were stable in M9 bacterial medium for 7 h at 37 °C. Further, NPs containing Captisol^® seem to prolong the release of associated drug. Bioassays against an E. coli Top 10 QS biosensor revealed that CS_70/5 NPs could inhibit QS up to 61.12%, while CS_70/20 NPs exhibited high antibacterial effects up to 88.32%. These results suggested that the interaction between NPs and the bacterial membrane could enhance either anti-QS or anti-bacterial activities.