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

Hao Thanh Nguyen,Francisco Goycoolea

doi:10.3390/molecules22111975

Abstract

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 CS70/5 and 330–600 nm with CS70/20, 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 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.

Highlights

The current poor efficacy of antibiotics to treat bacterial disease, due to the increasing widespread emergence of resistance, highlights the urgent need for alternative therapeutic strategies
This method is based on the ionic interaction between the positively charged CS and the negatively charged TPP and/or SBEβCD, and the ability of CS to form inter- and intra-molecular linkages with poly-anions resulting in the formation of colloidal particles
We have investigated the influences of free quercetin, chitosan, Captisol®, unloaded and quercetin-loaded nanoparticles at different concentrations to the responses of AHL-regulated biosensor strain, E. coli Top 10, regarding the evolution of the fluorescence intensity and the bacterial growth

Summary

Introduction

The current poor efficacy of antibiotics to treat bacterial disease, due to the increasing widespread emergence of resistance, highlights the urgent need for alternative therapeutic strategies. Rather than focusing on targeting bacteria either by bactericidal or bacteriostatic agents, targeting their virulence and associated factors, seems a more promising alternative approach. Such virulence factors are required for infection (e.g., toxin function and delivery, regulation of virulence expression and bacterial adhesion); they seem to be preserving the endogenous host microbiome and impose less selective pressure on pathogenic bacteria and in theory, decrease resistance [1]. Many bacteria use a cell-cell communication process termed quorum sensing (QS) to communicate, coordinately regulate their gene expression and synchronise their collective social behaviours, such as biofilm formation, bioluminescence and secretion of virulence factors [2,3]. QS is not essential for Molecules 2017, 22, 1975; doi:10.3390/molecules22111975 www.mdpi.com/journal/molecules

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