A Novel In Situ Gelling System of Quercetin/ Sulfobutyl-Ether-b-Cyclodextrin Complex-Loaded Chitosan Nanoparticles for the Treatment of Vulvovaginitis

Vulvovaginitis is a growing concern worldwide because of increasing drug resistance, drug toxicity, low bioavailability, and limitations of topical administration. The purpose of the study was to develop a novel mucoadhesive in situ gel of quercetin–cyclodextrin (CD)-loaded chitosan nanoparticles (NPs) for the treatment of vulvovaginitis. In this work, an innovative association between mucoadhesive (chitosan) and thermosensitive polymers (poloxamer 188 and 407) was used to treat vulvovaginitis. The formulation showed compatible pH (4.08) and a desired rheological behavior (viscosity—158.9 cps at 25.9°C, gelation temperature—37°C, and gelation time—65 s) suitable for vaginal application. The quercetin/sulfobutyl-ether-b-cyclodextrin-loaded chitosan NPs (QCD-NPs), prepared by the ionic-gelation method, showed higher in vitro antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa compared with the quercetin solution because of the ionic interaction between chitosan NPs and bacteria. Moreover, upon incorporating the QCD-NP in in situ gel, the clearance from the vagina might further reduce and longer residence can be achieved at the site of vaginal infection because of sol–gel transition at body temperature. The developed formulation was confirmed to be biocompatible, nonirritant (hen’s egg chorioallantoic membrane assay), and bioadhesive (mucoadhesion test) with good antimicrobial efficacy and sustained drug release profile, paving the path for improved therapeutic interventions in the treatment of vulvovaginitis.