Hydrogel-Delivered Standardized Pomegranate (Punica granatum) Extract Suppresses Quorum Sensing and Disrupts the Biofilm Structure in Pseudomonas aeruginosa.

Abstract

Pomegranate (Punica granatum) peel is a rich source of polyphenols with recognized bioactivities. This study evaluated the quorum sensing (QS)-inhibitory and anti-biofilm properties of a standardized pomegranate extract, as well as its major ellagitannins (punicalagin and ellagic acid), against Pseudomonas aeruginosa, an important opportunistic pathogen associated with multidrug-resistant infections. Using the P. aeruginosa strain (ATCC 27853) and the QS biosensor Chromobacterium violaceum, the pomegranate extract and punicalagin (MIC = 0.5 and 0.1 mg/mL, respectively) suppressed the production of QS-regulated virulence factors (pyocyanin >80%, rhamnolipids >60%), inhibited bacterial motility, and disrupted biofilm formation (>70%) without inducing resistance. Cytotoxicity assays demonstrated the favorable cytocompatibility of the extract in mammalian cells. To enable localized delivery, a mechanically robust polyvinyl alcohol-chitosan (PVA-CS) hydrogel was developed. Structural characterization revealed a porous, hydrogen-bond-stabilized structure with enhanced thermal stability, favorable swelling behavior, and excellent moisture retention. Under simulated infection conditions, the extract-loaded hydrogel (P3C2P) significantly inhibited bacterial growth, attenuated virulence production, and suppressed both motility and biofilm formation. These findings demonstrate a triple-action anti-infective mechanism-mediated by punicalagin, which concurrently targets virulence, motility, and biofilm formation. This work establishes a natural product-based hydrogel platform with significant translational potential for wound management and antimicrobial applications.