Novel Buccal Xanthan Gum-Hyaluronic Acid Eutectogels with Dual Anti-Inflammatory and Antimicrobial Properties.

Abstract

Buccal drug delivery systems often struggle with poor drug solubility, limited adhesion, and rapid clearance, leading to suboptimal therapeutic outcomes. To address these limitations, we developed a novel hybrid eutectogel composed of xanthan gum (XTG), hyaluronic acid (HA), and a Natural Deep Eutectic Solvent (NADES) system (choline chloride, sorbitol, and glycerol in 2:1:1 mole ratio), incorporating 2.5% ibuprofen (IBU) as a model drug. The formulation was optimized using a face-centered central composite design to enhance the rheological, textural, and drug release properties. The optimized eutectogels exhibited shear-thinning behavior (flow behavior index, n = 0.26 ± 0.01), high mucoadhesion (adhesiveness: 2.297 ± 0.142 N·s), and sustained drug release over 24 h, governed by Higuchi kinetics (release rate: 237.34 ± 13.61 μg/cm²/min^1/2). The ex vivo residence time increased substantially with NADES incorporation, reaching up to 176.7 ± 23.1 min. An in vivo anti-inflammatory evaluation showed that the eutectogel reduced λ-carrageenan-induced paw edema within 1 h and that its efficacy was sustained in the kaolin model up to 24 h (p < 0.05), achieving comparable efficacy to a commercial 5% IBU gel, despite a lower drug concentration. Additionally, the eutectogel presented a minimum inhibitory concentration for Gram-positive bacteria of 25 mg/mL, and through direct contact, it reduced microbial viability by up to 100%. Its efficacy against Bacillus cereus, Enterococcus faecium, and Klebsiella pneumoniae, combined with its significant anti-inflammatory properties, positions the NADES-based eutectogel as a promising multifunctional platform for buccal drug delivery, particularly for inflammatory conditions complicated by bacterial infections.