Dual-drug carboxymethyl chitosan hydrogel: Development, characterization, and in vitro evaluation for periodontal therapy

Abstract

Dual-drug delivery systems offer a novel approach to overcoming the complex challenges of periodontal disease treatment. This study aimed to develop and evaluate a carboxymethyl chitosan-based hydrogel incorporating doxycycline and atorvastatin for local delivery in periodontal therapy. The hydrogel formulations were characterized through Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and electron microscopy to assess their structural and physicochemical properties. The hydrogels were evaluated for drug loading efficiency and drug release profiles, antimicrobial activity, and cytotoxicity. The optimized formulation, containing 25 % atorvastatin and 75 % doxycycline, demonstrated a sustained and controlled release profile over 72 h, ensuring prolonged therapeutic effects. It exhibited significant antibacterial efficacy, particularly against Porphyromonas gingivalis, a keystone pathogen in periodontal disease, with inhibition zones reaching 54 ± 1.53 mm. Cytotoxicity assays on human keratinocyte cells (HaCaT) confirmed high biocompatibility, with over 97 % cell viability for the optimized formulation, whereas formulations with higher atorvastatin content exhibited increased cytotoxicity. These findings highlight the potential of this dual-drug hydrogel system as a promising localized treatment strategy for periodontal disease, offering controlled drug release, potent antimicrobial activity, and favorable biocompatibility. Future in vivo and clinical studies are warranted to validate its therapeutic efficacy and translational potential.

Keywords: Atorvastatin; Chitosan; Doxycycline; Dual-drug delivery systems; Hydrogels; Local drug delivery; Periodontal disease.