pH-Responsive Chlorhexidine-Loaded MSN@Chitosan/Alginate Nanocomposite for Controlled Antibacterial Delivery in Periodontal Applications

Abstract

Periodontal infections require effective local antimicrobial therapy capable of maintaining therapeutic drug concentrations at the site of infection while minimizing premature drug loss and potential systemic exposure. In this study, a pH-responsive chlorhexidine (CHX)-loaded mesoporous silica nanoparticle-based nanocomposite functionalized with chitosan and alginate (MSN@CS/ALG) was developed for controlled local antimicrobial delivery in periodontal applications. CHX-loaded MSN was prepared by an adsorption-based approach and subsequently coated with chitosan and alginate using different polymer concentrations. Nine formulations were prepared and evaluated based on particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), loading capacity (LC), and preliminary drug-release behavior. The optimized formulation was further investigated for pH-responsive CHX release, release kinetics, antibacterial activity against Porphyromonas gingivalis, and cytocompatibility. The optimized MSN@CS/ALG formulation exhibited a particle size of 161.7±3.6 nm, PDI of 0.19±0.01, zeta potential of −8.9±1.0 mV, EE of 88.7±1.2%, and LC of 20.4±0.7%. CHX release was strongly dependent on environmental pH, reaching 82.6±2.3%, 68.9±2.1%, and 49.7±1.9% after 48 h at pH 5.5, 6.5, and 7.4, respectively. Release kinetics were best described by the Korsmeyer-Peppas model, indicating combined diffusion and polymer relaxation mechanisms. The optimized formulation retained considerable antibacterial activity, with an inhibition zone of 18.6±0.7 mm and a MIC of 8 μg/mL against P. gingivalis. Cytocompatibility was favorable, with cell viability remaining above 87% after 48 h at concentrations up to 250 μg/mL. The developed MSN@CS/ALG nanocomposite demonstrated pH-responsive and sustained CHX delivery together with antibacterial activity and acceptable cytocompatibility, suggesting its potential as a localized delivery platform for periodontal applications. Further in vivo studies are required to confirm its therapeutic efficacy and long-term safety.