Chronic periodontitis is characterized by
inflammation of periodontal tissues, leading to
bone resorption and
tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of
tetracycline was proven to be effective in controlling localized periodontal
infection without apparent side effects. Previous studies suggested that
lovastatin has a significant role in new bone formation; however, the local delivery of
lovastatin might enhance its
therapeutic effects. A number of local delivery devices have been developed recently, including
poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-
lovastatin-
chitosan-
tetracycline nanoparticles, which allows the sequential release of
tetracycline and
lovastatin to effectively control local
infection and promote bone regeneration in
periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of
tetracycline and
lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and
alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-
lovastatin-
chitosan-
tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased
alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative
therapy.