Development and in vitro evaluation of chitosan based system for local delivery of atorvastatin for treatment of periodontitis

Abstract

In recent years, statin group drugs have been widely investigated in treatment of periodontal diseases due to their anti-inflammatory effect. The efficacy of statins can be enhanced by local administration into the periodontal pocket by appropriate delivery systems. The aim of our study was to develop a bioadhesive delivery system for local delivery of atorvastatin in treatment of periodontal disease. For this purpose, gel formulations were prepared using different types of chitosan (base and water soluble) and viscosity, bioadhesivity and syringeability of the gels as well as in vitro drug release properties were investigated vitro. Furthermore, anti-inflammatory effect of the formulations was studied in vitro using tumor necrosis factor (TNF)-alfa induced human gingival fibroblast (hGF) cells. Release of proinflammatory (IL-1β, IL-6, IL-8) and anti-inflammatory (TGF-β1, TGF-β2, TGF-β3, IL-10) cytokines were measured after incubating the hGF cells with the formulations. The viscosity of the formulations was found to be suitable for a local application into periodontal pocket. In presence of drug, bioadhesive property of the formulations was found to increase, and bioadhesion force was within the range, which would retain the delivery system at the application site, subsequently maintain drug levels at desired amount for longer period of time. The release of atorvastatin from the gels was found to be slower than that of the solution. The cytokine levels were found to decrease following application of the formulations, and anti-inflammatory effect was observed to enhance in presence of chitosan. No significant differences were found between base and water-soluble chitosan.