Chitosan Based Novel Mucoadhesive Formulations Against Bacterial

Abstract

Bacterial vaginosis (BV) is a recurring, chronic infection that is difficult to treat due to newlinethe limited bioavailability of antimicrobials within vaginal epithelial cells. Vaginal newlineadministration, because of lower dosing and systemic exposure, offers a viable option for newlinetreating vaginal infections and related secondary complications. In this study, newlineMetronidazole (MTZ)-loaded chitosan nanoparticles (MCSNP) were synthesized newlineemploying phytic acid (PA) or borax (BX) or tannic acid (TA) as an antimicrobial newlinecrosslinking agent as a novel strategy for treating bacterial vaginosis. The crosslinkers newlineare known to have antibacterial, antifungal, and anti-inflammatory properties. The newlineprepared nanoparticles were characterized for size, shape, surface charge, compatibility, newlinecytotoxicity, biofilm inhibition, and in-vitro/in-vivo antimicrobial activities. newlineMorphological examination revealed that nanoparticles generated from 0.535% w/v newlinechitosan and 0.112% w/v PA were non-spherical, discontinuous, and irregular, with zeta newlinepotential ranging from 25.00±0.45 to 39±0.7. The results of DSC and XRD newlinedemonstrated no change in the physical state of the drug in the finished formulations. newlineThe optimized formulation demonstrates a cumulative drug release of about 98±1.5% newlinewithin 8 hours. Antimicrobial studies demonstrated that the optimized formulation had newlineenhanced efficacy against acid-adapted BV pathogens, with a MIC value of 0.9±0.1 newlineand#956;g/mL. Compared to the MTZ alone, the in-vivo antibacterial results of in the case of newlinedeveloped nanoparticles showed a four-fold reduction in bacterial count in female Swiss newlinealbino mice. These PA crosslinked nanoparticles demonstrated an antifungal effect with newlinea minimum inhibitory concentration (MIC) of 140±2.2 and#956;g/mL, maintaining cell viability newlineat approximately 90% at the MIC value and reducing cytokine levels. Additionally, the newlinenanoparticles reduced ergosterol content and exhibited a 62% ±1.2 reduction in biofilm newlinesusceptibility, as supported by colony-forming unit (CFU) and XTT assays newlinefurthermore, treatment with n