Biopolymeric Composite Films of Hyaluronic Acid and Gellan Gum for Localized and Sustained Azithromycin Delivery in...

This study reports the development of azithromycin-loaded polymeric films (AZF) composed of gellan gum (GG) and hyaluronic acid (HA) for localized periodontal drug delivery. A 3² full factorial design was employed to optimize formulation variables and assess critical attributes influencing film performance. The films exhibited uniform thickness (0.13-0.16 mm), high folding endurance (> 300 folds), and a physiologically compatible surface pH (6.8-7.0). Increasing HA content significantly enhanced swelling and drug release, with all formulations having achieved high drug-loading efficiencies (92-100%). In vitro drug release studies revealed a biphasic release profile, an initial burst for rapid antimicrobial action followed by sustained release over 72 hours. Kinetics modeling using the Peppas-Sahlin equation indicated contributions from both Fickian diffusion and polymer relaxation. AFM, SEM and XTM confirmed the films' porous, uniform microstructure supporting sustained release behavior. AZF exhibited significantly superior antibacterial efficacy against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, compared to standard azithromycin and metronidazole discs. The localized, sustained drug delivery effectively overcomes limitations of systemic antibiotic therapy, including poor site retention and the need for systemic exposure. These findings support the potential of GG-HA films as biodegradable, patient-compliant platforms for targeted periodontal drug delivery, offering improved therapeutic outcomes and addressing biological barriers to effective treatment.