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Dioxadet-loaded nanogels as a potential formulation for glioblastoma treatment

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Abstract

Glioblastoma multiforme is a fast-growing malignant brain tumor with poor prognosis and low survival rate. Here we investigated the potential use of anticancer drug dioxadet loaded into nanogels for glioma treatment. We used block copolymer of polyethylene glycol and polymethacrylic acid for synthesis of dioxadet carriers and two types of cross-linking agents: non-degradable ethylenediamine and biodegradable cystamine, containing disulfide bond. We analyzed physicochemical properties of nanoparticles, their loading capacity, cytotoxicity of drug-loaded nanogels, and also their internalization into glioma cells. We found the optimal conditions that promote the efficient loading of the drug. We demonstrated that dioxadet loaded nanogels have relatively high level of loading capacity (>35% w/w) and loading efficiency (>75%). We shown that nanogels with the biodegradable cross-links prone to dissociate under reducing conditions (glutathione) that allow to decrease IC50 values of the drug compared to the nanogels with ethylendiamine cross-links. This stimuli-sensitive behavior of nanogels could be beneficial for tumor treatment. Confocal analysis of glioma cells demonstrated that both types of nanogels accumulate in cells and localize in lysosomes. These results indicate that loading of dioxadet into nanoparticles can improve its performance; such formulation has a potential for further studies and practical applications.

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Acknowledgements

We thank Anna Gabashvili for the help with cells for confocal microscopy. All authors declare that they have no conflict of interest. This article does not contain any studies with human and animal subjects performed by any of the authors. The study was supported by grant from Russian Scientific Foundation 14-15-00698.

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Authors and Affiliations

  1. Faculty of Materials Science, M.V. Lomonosov Moscow State University, Moscow, Russia

    Roman Voeikov

  2. Department of Fundamental and Applied Neurobiology, Serbsky National Medical Research Center for Psychiatry and Narcology, Ministry of Health and Social Development of the Russian Federation, Moscow, Russia

    Roman Voeikov, Tatiana Abakumova, Nadezhda Grinenko, Pavel Melnikov, Vladimir Chekhonin & Natalia Nukolova

  3. Group of Cancer Chemoprevention, N.N. Petrov Research Institute of of the Ministry of Health of the Russian Federation, St. Petersburg, Russia

    Vladimir Bespalov & Alexander Stukov

  4. Department of Medical Nanobiotechnology, Pirogov Russian State Medical University, Moscow, Russia

    Vladimir Chekhonin & Natalia Nukolova

  5. Department of Chemical Enzymology, Faculty of Chemistry, M.V. Lomonosov Moscow State University, Moscow, Russia

    Natalia Klyachko

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  1. Roman Voeikov
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  2. Tatiana Abakumova
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  4. Pavel Melnikov
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  5. Vladimir Bespalov
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  9. Natalia Nukolova
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Correspondence to Natalia Nukolova.

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Voeikov, R., Abakumova, T., Grinenko, N. et al. Dioxadet-loaded nanogels as a potential formulation for glioblastoma treatment. Journal of Pharmaceutical Investigation 47, 75–83 (2017). https://doi.org/10.1007/s40005-016-0294-4

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  • DOI: https://doi.org/10.1007/s40005-016-0294-4

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