An SH-BDDE crosslinked hydrogel for sustained paeonol delivery: enabling long-lasting dual antibacterial and antiinflammatory action

Abstract In this work, a novel paeonol-loaded hydrogel was synthesized to overcome disadvantages of poor water solubility and high volatility of free paeonol, and satisfy potential application in toothpaste. Hydrogels were firstly prepared from sodium hyaluronate (SH) and 1,4-butanediol diglycidyl ether (BDDE), and characterized comprehensively. The optimal hydrogel formulation was selected based on its closeness to the texture profile analysis of toothpaste: 3 g SH and 0.15 g BDDE in 20 g 1% NaOH solution at 30 °C for 3.5 h, followed by 24 h hydration. Extensive physiochemical analysis suggested a highly stable crosslinked microstructure, good mechanical properties and water holding capacity, and tunable swelling behavior of hydrogel, which could support effective encapsulation and sustained release for drugs. Compared with free paeonol, antibacterial duration of hydrogel paeonol-loaded was significantly prolonged. Cell antiinflammatory analysis further verified that paeonol-loaded hydrogel could reduce the contents of tumor necrosis factor- α (TNF- α ), interleukin-6 (IL-6) and interleukin-1 β (IL-1 β ). The results of this study demonstrate that the developed hydrogel paeonol-loaded synergistically combines excellent toothpaste applicability, efficient antibacterial and antiinflammatory activities, and long-term drug release ability, which provides a new and promising strategy for paeonol to be used as a potential active ingredient in the adjuvant treatment of periodontitis.