Development of diclofenac and metronidazole thermo-responsive mucoadhesive in situ gel for periodontal drug delivery

Abstract

Periodontitis is a chronic inflammatory disease driven by anaerobic bacterial biofilms within periodontal pockets. Conventional oral dosage forms exhibit limitations in pocket retention and sustained drug exposure, necessitating more effective local delivery strategies. This study aimed to develop and optimize a thermo-responsive mucoadhesive in situ gel containing diclofenac (DIC) and metronidazole (MTZ) using a Poloxamer 407/Poloxamer 188 binary system for periodontal drug delivery. A Central Composite Design (CCD) was employed to optimize gelation temperature (Tgel), yielding a significant quadratic model (p < 0.001, R² = 98.81%). The optimized formulation (P407 16.44% w/w; P188 7.93% w/w) exhibited Tgel = 33.68 ± 0.45 °C, suitable for syringe-based administration into periodontal pockets followed by in situ solidification at physiological temperature. Drug-loaded formulations demonstrated enhanced mucoadhesive strength compared with the blank gel. The BSA denaturation assay confirmed significant anti-inflammatory activity in DIC-containing formulations, with the dual-drug gel (G-DM) achieving 82.13% inhibition relative to the poloxamer matrix baseline. Antimicrobial testing demonstrated inhibitory activity against Porphyromonas gingivalis, Streptococcus mutans, and MRSA. In vitro drug release showed sustained, diffusion-controlled release of both drugs over 24 hours, markedly superior to the solution control. These findings support the potential of this binary poloxamer-based gel as a dual-action local delivery platform for periodontitis management.