Formulation and Evaluation of in situ Oral Gels Containing Chlorhexidine Gluconate and Curcumin for Periodontitis

Abstract

Background: Periodontitis is a chronic inflammatory disease associated with bacterial plaque accumulation, and its treatment is often limited by the inadequate retention of antimicrobial agents within periodontal pockets. Thermo-responsive in situ gels offer a promising strategy for localized and sustained drug delivery. Objectives: To formulate and evaluate thermo-reversible in situ gels containing Chlorhexidine Gluconate (CHX) and Curcumin (CUR) for periodontal therapy and compare their performance with commercially available formulations. Materials and Methods: Thermo-sensitive hydrogels were prepared using the cold method with Poloxamer 407 as the primary polymer, along with Hydroxypropyl Methylcellulose (HPMC) and polyethylene glycol 400 (PEG 400). Following overnight hydration at 4ºC, CHX or CUR was incorporated into the polymeric matrix. The formulations were evaluated for gelation temperature, pH, viscosity, drug content, in vitro drug release, and antimicrobial activity using the agar well diffusion method. The optimized formulations were compared with Hexigel® and Curenext® gel. Results: The optimized formulation (P4) exhibited suitable gelation temperature, viscosity, and uniform drug loading. The CHX-loaded gel demonstrated sustained drug release, achieving 74.2% release over 49 hr, whereas the CUR-loaded gel released 98.18% of the drug within 24 hr. Antimicrobial studies revealed that the CHX gel showed the highest inhibitory activity, outperforming Hexigel®, while the CUR gel exhibited greater efficacy than Curenext® gel. Conclusion: The developed thermo-responsive in situ gels showed superior sustained-release characteristics and antimicrobial efficacy compared with commercial formulations. These findings suggest that CHX- and CUR-loaded in situ gels are promising candidates for effective localized management of periodontitis.