Hyaluronic Acid Modified Risedronate and Teriparatide Co-loaded Nanocarriers for Improved Osteogenic Differentiation of Osteoblasts for the Treatment of Osteoporosis

Background: Owing to its multifactorial intricate pathogenesis, combined therapeutic regimen is considered appropriate for the treatment of osteoporosis. However, a multi-drug regimen is also associated with adverse effects due to the non-specific distribution of drugs. Therefore, the present study aims for efficient codelivery of risedronate (RDN) (a potent bone anti-resorptive drug) and teriparatide (TPD) (anabolic agent) as hyaluronic acid (HA)-modified chitosan nanoparticles (NPs). Methods: RDN/TPD NPs were synthesized using the high- pressure homogenization – solvent evaporation technique. The fabricated NPs were then characterized and optimized for suitable physicochemical characteristics. The optimized NPs were then evaluated for bone remodeling potential via assessment of time-mannered modulation in proliferation, differentiation, and mineralization of osteoblasts. Results: Results showed that HA-RDN/TPD NPs exhibited excellent physicochemical characteristics (nanoscopic size, stable zeta potential, high entrapment efficiency, and smooth spherical shape) and remained stable upon storage in the refrigerator. Assessment of various aspects of the cell growth cycle (i.e., proliferation, differentiation, and mineralization) evidenced promising bone regeneration efficacy of HA-RDN/TPD NPs. Conclusion: This new strategy of employing simultaneous delivery of anti-resorptive and bone-forming agents would open new horizons for scientists, researchers, and healthcare providers as an efficient pharmacotherapy for the treatment of osteoporosis.