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Hydroxyapatite-dextran methacrylate core/shell hybrid nanocarriers for combinatorial drug therapy

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Abstract

In this study, a hybrid dual drug-loaded hydroxyapatite-oxidized dextran methacrylate core–shell nanocarrier was formulated and explored for combinatorial delivery of doxorubicin (DOX) and methotrexate (MTX) to bone cancer. The synthesized nanocarrier was well characterized by different techniques. In vitro drug release studies in both acidic (pH 5) and alkaline (pH 7.4) conditions showed sequential release of MTX followed by DOX in a sustained manner for 10 days. Biocompatibility and cytotoxicity studies performed using drug-loaded nanoparticles (NPs) on fibroblast L929 cells and osteosarcoma MG63 cells (OMG63) showed that the NPs were highly biocompatible and showed concentration-dependent toxicity. Gene expression studies in OMG-63 cells exhibited the upregulation of caspase-3 and BAX which confirmed the apoptosis induced by dual drug-loaded NPs. The nanocarrier is expected to be a potential bone void filling material, as well as a platform for sequential delivery of DOX and MTX for the treatment of bone cancer.

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Acknowledgments

The authors thank Prof. Nitish R. Mahapatra for providing cell culture facility and thanks are due to Mr. Abrar Ali Khan and Mrs. Hemalatha who helped in gene expression studies. The authors thank Professor Sakthi Kumar of Toyo University, Japan for the TEM analysis. The authors also thank Central XRD Facility and Sophisticated Analytical Instrument Facility (SAIF) of IIT Madras for analytical support. This research did not receive any specific grant from any funding agencies in the public, commercial or not-for-profit sectors.

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  1. A. Jayakrishnan

    Present address: Raja Ramanna Fellow, Rajiv Gandhi Centre for Biotechnology, Jagathy, Trivandrum, 695 014, Kerala, India

Authors and Affiliations

  1. Biomaterials Laboratory, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600 036, Tamil Nadu, India

    S. Ram Prasad & A. Jayakrishnan

  2. Medical Materials Laboratory, Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai, 600 036, Tamil Nadu, India

    S. Ram Prasad & T. S. Sampath Kumar

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  1. S. Ram Prasad
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Correspondence to A. Jayakrishnan or T. S. Sampath Kumar.

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Ram Prasad, S., Jayakrishnan, A. & Sampath Kumar, T.S. Hydroxyapatite-dextran methacrylate core/shell hybrid nanocarriers for combinatorial drug therapy. Journal of Materials Research 35, 2451–2465 (2020). https://doi.org/10.1557/jmr.2020.193

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