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-beta-cyclodextrin (Captisol (R)) 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 CS70/5 and 330-600 nm with CS70/20, had low polydispersity index (<0.25) and highly positive zeta potential ranging from zeta similar to+31 to +40 mV. Quercetin, a hydrophobic model flavonoid, could be incorporated proportionally with increasing amounts of Captisol (R) in the NPs formualtion, without altering significantly its physicochemical properties. Elemental analysis and FTIR studies revealed that Captisol (R) and quercetin were effectively integrated into the NPs. These NPs were stable in M9 bacterial medium for 7 h at 37 degrees C. Further, NPs containing Captisol (R) seem to prolong the release of associated drug. Bioassays against an E. coli Top 10 QS biosensor revealed that CS70/5 NPs could inhibit QS up to 61.12%, while CS70/20 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.