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Methotrexate-Loaded Chitosan- and Glycolchitosan-Based Nanoparticles: A Promising Strategy for the Administration of the Anticancer Drug to Brain Tumors

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Abstract

Brain tumor treatment employing methotrexate (MTX) is limited by the efflux mechanism of Pg-p on the blood–brain barrier. We aimed to investigate MTX-loaded chitosan or glycol chitosan (GCS) nanoparticles (NPs) in the presence and in the absence of a coating layer of Tween 80 for brain delivery of MTX. The effect of a low Tween 80 concentration was evaluated. MTX NPs were formulated following the ionic gelation technique and size and zeta potential measurements were acquired. Transport across MDCKII-MDR1 monolayer and cytotoxicity studies against C6 glioma cell line were also performed. Cell/particles interaction was visualized by confocal microscopy. The particles were shown to be cytotoxic against C6 cells line and able to overcome MDCKII-MDR1 cell barrier. GCS-based NPs were the most cytotoxic NPs. Confocal observations highlighted the internalization of Tween 80-coated fluorescent NPs more than Tween 80-uncoated NPs. The results suggest that even a low concentration of Tween 80 is sufficient for enhancing the transport of MTX from the NPs across MDCKII-MDR1 cells. The nanocarriers represent a promising strategy for the administration of MTX to brain tumors which merits further investigations under in vivo conditions.

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ACKNOWLEDGMENTS

This project was financed by Università degli Studi di Bari (Progetti di Ateneo 2008). We thank Dr. Antonella Loverre (Dipartimento di Emergenza Trapianti di Organi, (D.E.T.O.) Bari Hospital, Bari, Italy) for interpretation of confocal microphotographs. We also thank Prof. Giuseppe Trapani (University of Bari) for helpful discussions.

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The authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of Bari, Aldo Moro, Via Orabona, 4, 70125, Bari, Italy

    Adriana Trapani & Nunzio Denora

  2. Department of Chemistry, University of Bari, Aldo Moro, Via Orabona, 4, 70125, Bari, Italy

    Giuliano Iacobellis

  3. Department of Pharmaceutics and Biopharmacy, Philipps-University, Ketzerbach 63, 35032, Marburg, Germany

    Johannes Sitterberg, Udo Bakowsky & Thomas Kissel

Authors
  1. Adriana Trapani
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  2. Nunzio Denora
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  3. Giuliano Iacobellis
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  4. Johannes Sitterberg
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  5. Udo Bakowsky
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  6. Thomas Kissel
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Correspondence to Adriana Trapani.

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Trapani, A., Denora, N., Iacobellis, G. et al. Methotrexate-Loaded Chitosan- and Glycolchitosan-Based Nanoparticles: A Promising Strategy for the Administration of the Anticancer Drug to Brain Tumors. AAPS PharmSciTech 12, 1302–1311 (2011). https://doi.org/10.1208/s12249-011-9695-x

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  • DOI: https://doi.org/10.1208/s12249-011-9695-x

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