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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
Authors:Pratigyan Dash  Sasmita Samal  Gyanendra Prasad Panda  Anna Maria Piras  Mamoni Dash
Institution:1. Institute of Life Sciences, DBT-ILS, ILS, Nalco Nagar Rd, Nalco Square, Chandrasekharpur, Bhubaneswar, Odisha, 751023 India

School of Biotechnology, KIIT University, KIIT Rd, Patia, Bhubaneswar, Odisha, 751024 India;2. Institute of Life Sciences, DBT-ILS, ILS, Nalco Nagar Rd, Nalco Square, Chandrasekharpur, Bhubaneswar, Odisha, 751023 India;3. Department of Pharmacy, University of Pisa, Via Bonanno Pisano, 12, Pisa, PI, 56126 Italy

Abstract:Osteosarcoma (OS) is a malignant tumor, fatal for pediatric patients who do not respond to chemotherapy, alternative therapies and drugs can provide better outcomes. Zoledronic acid (Zol) belonging to the class of bisphosphonates (BPs) has a direct antitumor ability to prevent Ras GTPases modification and stimulate apoptosis. Despite advances in maintaining balance in skeletal events and direct anticancer properties, Zol causes 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 native Zol. The cytotoxic effect is evaluated on bone cancer cells and healthy bone cells with three different cell lines namely, K7M2 (mouse OS cell line), SaOS2 (human OS cell line), and MC3T3E1 (healthy cell counterpart). It is observed that Zol nanoformulation is uptaken more (95%) in K7M2 whereas in MC3T3E1, the percent population internalizing nanoparticles (NPs) is 45%. Zol has a sustained release of 15% after 96 h from the NP which leads to a rescuing effect on the normal pre-osteoblast cells. In conclusion, it can be stated that Zol nanoformulation can be used as a good platform for a sustained release system with minimum side effects to normal bone cells.
Keywords:cytotoxicity  drug delivery  nanoparticles  osteosarcoma  poly(lactic-co-glycolic acid)
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