Synthesis, characterization and evaluation of tinidazole-loaded mPEG–PDLLA (10/90) <i>in situ</i> gel forming system for periodontitis treatment

<p>Traditional <i>in situ</i> gel forming systems are potential applications for parenteral administration but always accompanied with burst release. To overcome this limitation, the tinidazole (TNZ)-loaded <i>in situ</i> gel forming system using a diblock copolymer, monomethoxy poly(ethylene glycol)–block-poly(d,l-lactide) (mPEG–PDLLA), was designed. The formulation of the mPEG–PDLLA-based TNZ <i>in situ</i> gel forming system contained 5% (w/w) TNZ, 0.4% glycerol, 5 ml <i>N</i>-methyl pyrrolidone (NMP) and 35% (w/w) mPEG–PDLLA. The <i>in situ</i> gel forming system showed sustained TNZ release over 192 h with low burst effect (around 7% in the first 8 h) in the <i>in vitro</i> release study. Additionally, <i>in vivo</i> studies were performed on rabbits with ligature-induced periodontitis, and the concentration of TNZ in the gingival crevicular fluid (GCF) as well as the pharmacokinetic parameters was calculated and the pharmacological effect of TNZ-loaded <i>in situ</i> gel forming (mPEG–PDLLA)-based system was found effective. Finally, histological studies revealed that the gel was a safe formulation with low irritation. The desirable drug release kinetics combined with the excellent <i>in vivo</i> characteristics highlight the potential of the gel in the treatment of periodontitis. Therefore, these results confirmed that the TNZ-loaded <i>in situ</i> gel forming mPEG–PDLLA-based system could reduce burst release of TNZ and act as a sustained-release and injectable drug depot for periodontitis treatment.</p