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The aim of this study was to develop a chitosan-based risedronate/zinc-hydroxyapatite intrapocket dental film (CRZHDF) for applications in the treatment of alveolar bone loss in an animal model of periodontitis. The physical characteristics (folding endurance, pH, mucoadhesive strength, risedronate content and release) of CRZHDF, exhibited results within the limit. X-ray diffraction analysis indicates reduced or disappeared crystallinity of risedronate and zinc-hydroxyapatite in presence of chitosan. Further, FTIR studies revealed stability of CRZHDF and compatibility between risedronate, zinc-hydroxyapatite and chitosan. Periodontitis was induced by Porphyromonas gingivalis-lipopolysaccharide injections around the mandibular first molar. We divided rats into 5 groups (12 rats/group): healthy, untreated periodontitis; periodontitis plus CRZHDF-A, periodontitis plus CRZHDF-B, and periodontitis plus chitosan film. After four weeks, blood samples and mandibles were obtained for biochemical, radiographic and histological analysis. Bone specific alkaline phosphatise activity and tartrate resistant acid phosphatase 5b was statistically lower in CRZHDF-A and CRZHDF-B groups as compared to the untreated periodontitis group (p < 0.0001). The expression of osteocalcin was statistically higher in CRZHDF-A and CRZHDF-B groups as compared to the untreated periodontitis group (p < 0.0001). Alveolar bone was intact in the healthy group. Local administration of CRZHDF resulted in significant improvements in the mesial and distal periodontal bone support (MPBS and DPBS, respectively) proportions (%), bone mineral density, and also reversed alveolar bone resorption when compared to the untreated periodontitis group (p < 0.001). The study reported here reveals that novel CRZHDF treatment effectively reduced alveolar bone destruction and contributes to periodontal healing in a rat model of experimental periodontitis.

A superior drug formulation capable of achieving efficient osteogenesis is in imperative demand for the treatment of osteoporosis. In the present study we investigated the potential of using novel risedronate-hydroxyapatite (HA) nanoparticle based formulation in an animal model of established osteoporosis. Nanoparticles of HA loaded with risedronate (NHLR) of various sizes (80-130 nm) were generated for bone targeted drug delivery. Three months after ovariectomy, 36 ovariectomized (OVX) rats were divided into 6 equal groups and treated with various doses of NHLR (500, 350 and 250 microg/kg intravenous single dose) and sodium risedronate (500 microg/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. One month after drug administration, the left tibia and femur were tested for bone mechanical properties and histology, respectively. In the right femur, bone density was measured by method based on Archimedes principle and bone porosity analyses were performed using X-ray imaging. NHLR (250 microg/kg) showed a significant increase in bone density and reduced bone porosity when compared with OVX control. Moreover, NHLR (250 microg/kg) significantly increased bone mechanical properties and bone quality when compared with OVX control. The results strongly suggest that the NHLR, which is a novel nanoparticle based formulation, has a therapeutic advantage over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model of postmenopausal osteoporosis.