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

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.

Chitosan Derivatives: Introducing New Functionalities with a Controlled Molecular Architecture for Innovative Materials

“…Finally, it should be noted that there is an increasing number of publications in which chitosan and cyclodextrin are used as important components in the preparation of nano-vehicles or stimuli-sensitive carriers [ 170 , 185 , 191 , 200 , 201 , 202 , 203 ].…”

Palladium Nanoparticles Functionalized with PVP-Quercetin Inhibits Cell Proliferation and Activates Apoptosis in Colorectal Cancer Cells

“…It was reported that in metastatic ovarian cancer cells, quercetin increases the level of proapoptotic molecules such as cytochrome c, Bid, Bad, Bax, caspase-3, and caspase-9, indicating the mitochondrialmediated apoptotic pathway [31]. Similar results have been described in prostate cancer; quercetin activates caspase-3 and caspase-9 triggering apoptotic mechanisms via the mitochondrial pathway [32].The NPs used as carriers for the delivery of quercetin into target cells have been evaluated in different diseases [33,34]. On the one hand, NPs alone offers a system that causes damage to specific cells by mechanisms such as oxidative stress, lipids and proteins oxidation, and high toxicity due to their physicochemical characteristic as the superficial charge [35].…”

<p>Quorum Quenching: A Potential Target for Antipseudomonal Therapy</p>

“…85 Suitable therapeutic compounds are not only required to display a low toxicity index, but also to have appropriate pharmacokinetic features for clinical usages. 86 Nanoparticles are also recognized as synthetic QSIs. However, more studies are required to explore these nanoparticles additionally.…”