Novel elastic nanovesicular hydrogel system: advancing metronidazole delivery for effective periodontitis management

Periodontitis, characterized by chronic gingival inflammation driven by polymicrobial biofilm formation, presents a significant therapeutic challenge due to the inherent difficulty of antimicrobial penetration through the biofilm matrix and limited drug retention.

To address these challenges, this study developed a metronidazole-loaded spanlastic-based mucoadhesive hydrogel (MTZ-SPLG) for direct intra-pocket delivery, designed to overcome biofilm barriers and prolong drug residence time. The spanlastics (SPL) formulation achieved optimal characteristics (93% EE, 0.168 PDI, 280.8 nm size) through Design Expert^® 13 optimization, utilizing Span 80 (15 mg/ml) and Tween 80 (6.5 mg/ml) with 4-min sonication in the ethanol injection process. FTIR analysis confirmed the absence of chemical interactions, while DSC and XRD demonstrated successful transformation of metronidazole (MTZ) from crystalline to amorphous form. The optimized metronidazole loaded spanlastics (MTZ-SPL) incorporated into a Carbopol^® hydrogel base, exhibited suitable intra-periodontal properties including homogeneity, appropriate pH, and optimal spreadability, with mucoadhesive strength of 2256.3 N/m².

In vitro studies at pH 6.8 revealed sustained drug release following Korsmeyer-Peppas model with Fickian diffusion, outperforming conventional MTZ formulations. The MTZ-SPLG formulation demonstrated superior antibacterial efficacy with the largest inhibition zones (29.0-30.5 mm), lowest MIC values (2.2-5.9 μg/mL), and highest biofilm inhibition (60-89%) and degradation (43.6-64.3%) across all tested pathogens. Despite lower permeation than MTZ-SPL, MTZ-SPLG achieved optimal tissue retention (81.6 μg/cm²).

Based on our study findings, the formulation significantly reduced inflammation and demonstrated superior efficacy in periodontitis treatment.