Multiparticulate based thermosensitive intra-pocket forming implants for better treatment of bacterial infections in periodontitis.

Considering alarming projections in the prevalence of periodontitis, following study was undertaken to develop chitosan-vanillin crosslinked microspheres loaded in-situ gel (MLIG) implants containing ornidazole and doxycycline hyclate for the treatment of pocket infections. Firstly, microspheres were formulated and optimized using response surface methodology for particle size <50 μm, entrapment efficiency >80%, in-vitro drug release (T80% ) >7 days and acceptable mucoadhesion. Further, MLIG were optimized for gelation temperature of 34-37 °C and viscosity <1000 cps respectively. FTIR, DSC and XRD graphs disclosed compatibility and alterations in crystallinity of drugs. In-vitro dissolution study demonstrated non-Fickian type of drug release mechanism for twelve days. Stability studies ascertained MLIG implants were sterilizable and stable for about 11.29 months on refrigeration. The formulations exhibited significant (p < 0.001) antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis, and were found biocompatible and biodegradable during preclinical studies. Ligature-induced periodontal rat model, corroborated significant growth (p < 0.05) of gingival tissue after two weeks. Clinical trials revealed, intra-pocket administration of MLIG along with SRP provided significant reduction in clinical parameters as compared to SRP alone. Conclusively, antimicrobials incorporated thermosensitive, biodegradable, mucoadhesive and syringeable MLIG implants appeared as better option for the treatment of periodontitis.