Polymeric Nanoformulation of Zoledronic Acid Rescues Osteoblasts From the Harmful Effect of its Native Form: An in-Vitro Investigation of Cytotoxic Potential on Osteoblasts and Osteosarcoma Cells.

Abstract

Osteosarcoma is a malignant tumor, fatal for pediatric patients who do not respond to chemotherapy, alternative therapies and drugs could provide better outcomes.Zoledronic acid belonging to the class of bisphosphonates (BP) has direct antitumor ability preventing Ras GTPases modification and stimulating apoptosis. Despite advances in maintaining balance in skeletal events and direct anticancer property, Zoledronic acid causes some cytotoxicity to normal healthy pre-osteoblast cells, hampering mineralization and differentiation. The study reports the preparation and evaluation of a nanoformulation that can diminish the existing drawbacks of administering native Zoledronic The cytotoxic effect is evaluated on bone cancer cells and healthy bone cells with 3 different cell lines namely, K7M2 (mouse osteosarcoma cell line), SaOS2 (human osteosarcoma cell line) and MC3T3E1 (healthy cell counterpart). It is observed that Zoledronic acid nanoformulation is uptaken more (95%) in K7M2 whereas in MC3T3-E1 the percent population internalizing NPs is 45%. Zoledronic acid has a sustained release of 15% after 96h from the nanoparticle which leads to a rescuing effect on the normal pre-osteoblast cells. In conclusion, we can state that Zoledronic acid nanoformulation can be used as a good platform for a sustained release system with minimum side effects to normal bone cells. This article is protected by copyright. All rights reserved.