Rosuvastatin/calcium carbonate co-precipitated nanoparticles: A novel synergistic approach enhancing local bone regeneration in osteoporotic rat model.

Abstract

This study aimed at preparing sustained release rosuvastatin (Ru) calcium carbonate (CC) co-precipitate nano-formulation for local intra-osseous application in osteoporotic rats. Nano-formulations were prepared by the co-precipitation method using different concentrations of polyvinyl alcohol (PVA) (0.2, 0.4, 0.6 %) as a stabilizer and equimolar ratios of calcium chloride and calcium carbonate (0.1, 0.3 or 0.5 M). Pre-formulation examination including; FTIR and X-ray diffraction confirmed the formation of CC nanoparticles in a crystalline structure that was preserved before and after loading with Ru. The optimized formula showing; PS of 105.71 ± 5.10 nm, PDI of 0.25 ± 0.02, ZP of -44.70 ± 0.09 mV, % EE of 60.16 ± 1.58 and a quasi-spherical nanoparticle with nano-deposition of Ru crystals adsorbed on them as seen under TEM and SEM, was then integrated in 20 % Pluronic gel. The Ru-gel exhibited good rheological behavior with a short gelation time of 20 sec and a sustained release pattern of 30 % for the optimized Ru/CC gel versus ≈ 90 % for the Ru/CC dispersion after 6 h. In-vivo, ovariectomy-induced osteoporotic rats were used to cause a bone defect in the tibial metaphysis. The drill-hole defects were then filled with the formulations under test and examined 30 days postoperatively. Through SEM-EDX scanning, histological assessments, and evaluation of bone metabolic markers, Ru/CC treatment significantly enhanced bone healing, improved bone microarchitecture, increased trabecular bone area, enhanced osteogenic gene expression, and reduced osteoclast activity. Experiments proved that Ru/CC successfully enhances osteogenesis and reduces osteoclastogenesis, proposing it as a promising therapeutic approach for enhancing bone regeneration in osteoporosis.