Locally delivered lovastatin-containing chitosan nanoparticles promote bone regeneration in rats

Hypolipidemic statins can stimulate osteoregeneration. However, such effects are observed only after administration methods that are unacceptable for patients (prolonged infusions or huge oral doses). The aim of our research was to compare the osteoregeneration effects of lovastatin administered alone as a common pharmaceutical formulation and as lovastatin-containing chitosan nanoparticles (LCCN) in a drill-hole model of bone damage in rats. White inbred rats were randomly divided into four groups: group 1 – intact rats; group 2 – rats with bone defect without treatment (control group); group 3 – rats with bone defect, which received common pharmaceutical formulation of lovastatin at doses of 0.1, 1.0 and 5.0 mg/kg; group 4 – rats, which received 0.1 mg/kg lovastatin in the form of lovastatin-containing chitosan nanoparticles (LCCN). A dental drill of 2.0 mm in diameter was used to form the tibial bone defect. Rats were sacrificed 3, 7, 14 and 28 days after bone defect formation. Calcium (Ca), phosphorus (P) and sialic acid concentrations, alkaline and acidic phosphatase activities, mineralization index, and collagenolytic activity were measured in blood serum. Computed tomography (CT) and histological study were used to estimate the regenerative processes in the bone. It was found that therapeutic doses of lovastatin (0.1 and 1.0 mg/kg) are ineffective for bone defect healing. Only high doses of lovastatin (5.0 mg/kg) promote osteoregeneration. LCCN were more efficient compared to lovastatin alone, as confirmed by CT examination of bone defects and significant changes of Ca, P, and sialic acid concentrations, alkaline and acidic phosphatase activities, mineralization index, and collagenolytic activity. Lovastatin-containing chitosan nanoparticles effectively enhance fracture healing in used preclinical model. This finding suggests the possibility that a similar approach may be effective in hastening fracture repair in humans