Design and development of novel hyaluronate-modified nanoparticles for combo-delivery of curcumin and alendronate: fabrication, characterization, and cellular and molecular evidences of enhanced bone regeneration

• Published in: International Journal of Biological Macromolecules
• Main Author: Dong J.; Tao L.; Abourehab M.A.S.; Hussain Z.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2018
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85048491780&doi=10.1016%2fj.ijbiomac.2018.05.116&partnerID=40&md5=754f1888e856215048525e809596c017

Osteoporosis is a medical condition of fragile bones with an increased susceptibility to fracture. Despite having availability of a wide range of pharmacological agents, prevalence of osteoporosis is continuously escalating. Owing to excellent biomedical achievements of nanomedicines in the last few decades, we aimed combo-delivery of bone anti-resorptive agent, alendronate (ALN), and bone density enhancing drug, curcumin (CUR) in the form of polymeric nanoparticles. To further optimize the therapeutic efficacy, the prepared ALN/CUR nanoparticles (NPs) were decorated with hyaluronic acid (HA) which is a well-documented biomacromolecule having exceptional bone regenerating potential. The optimized nanoformulation was then evaluated for bone regeneration efficacy by assessing time-mannered modulation in the proliferation, differentiation, and mineralization of MC3T3-E1 cells, a pre-osteoblastic model. Moreover, the time-mannered expression of various bone-forming protein biomarkers such as bone morphogenetic protein, runt related transcription factor 2, and osteocalcin were assessed in the cell lysates. Results revealed that HA-ALN/CUR NPs provoke remarkable increase in the proliferation, differentiation, and mineralization in the ECM of MC3T3-E1 cells which ultimately leads to enhanced bone formation. This new strategy of employing simultaneous delivery of anti-resorptive and bone forming agents would open new horizons for scientists as an efficient alternative pharmacotherapy for the management of osteoporosis. © 2018