Formulation and Biological Evaluation of Quorum Sensing Inhibitor-Based Nanoemulsion against Resistant Pseudomonal Infections

Abstract

Antimicrobial resistance has raised a serious concern due to the lack of therapeutics to control pathogenic infections. Pseudomonas aeruginosa is considered a multidrug-resistant pathogen and a leading cause of hospital-acquired infections. Anti-virulence approach mainly focuses on targeting bacterial virulence despite its growth and proves effective against such drug-resistant pathogens. In this study, we select a novel flavonoid compound, 7,8-dihydroxyflavone (DHF), which has been reported as a quorum sensing inhibitor (QSI) of P. aeruginosa, performed its in-silico studies to observe its binding affinity and potential interactions with the target protein (2UV0) and further developed it as a nano drug formulation (DHF-NF), and performed its in-vitro and in-vivo evaluation. The prepared DHF-NF was examined for its efficacy in the prevention of wound-associated surface infections of P. aeruginosa in rats. The DHF-NF was prepared by using homogenization and examined for several physical parameters. The prepared DHF-NF had a spherical shape and smooth topology. The microbiological assays demonstrated the inhibitory potential of DHF-NF in a dose-dependent manner. The histological analysis of Pseudomonas infected tissue of rat skin showed significant activity in animal group treated with DHF-NF as compared to control groups. The microbiological and in-vivo evaluation results revealed that the compound, DHF, showed strong inhibitory potential and suggest that the DHF-NF could be utilized as novel anti-QS and anti-biofilm therapeutics against Pseudomonal surface infections.