Mechanistic Insights into Moxifloxacin HCl Permeability from Nitrocellulose-Based In Situ Gels via Confocal Imaging and DFT Modeling.

This study reports the development and multiscale evaluation of a nitrocellulose (Nc)-based in situ gel (ISG) system for localized delivery of moxifloxacin HCl (Mx) in periodontitis therapy. The formulations, composed of 15% w/w Nc dissolved in glycerol formal (Gf) or dimethyl sulfoxide (DMSO), exhibited rapid gelation within 1-3 min upon exposure to simulated crevicular media. SEM revealed solvent-dependent matrix morphology, with DMSO-based ISG forming denser and more porous structures, while Gf-based systems showed smoother, lamellar-like architectures. In vitro drug release through porcine mucosa membrane studies using Franz diffusion demonstrated sustained release profiles. CLSM imaging confirmed depth-restricted tissue penetration of sodium fluorescein (Sf), with fluorescence limited to < 50 µm in Nc-based ISGs versus > 100 µm Sf-loaded solvent controls. Drug distribution analysis further showed increased retention in Nc matrix and porcine mucosa in which Nc-formulations retarded diffusion into the receptor medium. DFT analysis revealed that Nc-Mx complex exhibited the most apparent binding energy (-2.43 eV) compared to Mx-solvent and Nc-solvent interactions, supporting a polymer-drug affinity-driven release mechanism. Collectively, these results establish Nc-based ISG as a promising platform for targeted mucosa-retentive delivery of antibiotics in periodontal therapy, combining tunable matrix formation with molecular-level control over drug diffusion.