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Ketoprofen-loaded polymeric nanocapsules selectively inhibit cancer cell growth in vitro and in preclinical model of glioblastoma multiforme

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Summary

Glioblastoma multiforme (GBM) is the worst and most common brain tumor, characterized by high proliferation and invasion rates. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted interest in recent years since they provide targeted delivery and may overcame the obstacle imposed by blood–brain barrier. Here we investigated the antitumoral effect of ketoprofen-loaded nanocapsules (Keto-NC) treatment on in vitro and in vivo glioma progression. We observed that Keto-NC treatment decreased selectively the cell viability of a panel of glioma cell lines, while did not exhibited toxicity to astrocytes. We further demonstrate that the treatment with sub-therapeutic dose of Keto-NC reduced the in vivo glioma growth as well as reduced the malignity characteristics of implanted tumors. Keto-NC treatment improved the weight, the locomotion/exploration behavior of glioma-bearing rats. Importantly, Keto-NC treatment neither induced mortality or peripheral damage. Finally, Ketoprofen also altered the extracellular nucleotide metabolism of peripheral lymphocytes, suggesting that antiinflammatory effects of ketoprofen could also be associated with the modulation of the adenine nucleotide metabolism in lymphocytes. Data indicate at first time the potential of Keto-NC as a promising therapeutic alterative to GBM treatment.

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Acknowledgments

We thank C. Perry, M. da Silva and S. Pereira for their excellent technical assistance; Dr A.M.O. Battastini for C6 cell line. This study was supported by the Brazilian agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS - Processo 10/0286-2). E.F. da Silveira and F.C. Teixeira were recipients of CAPES Master fellowship.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brazil

    Elita F. da Silveira, Fernanda C. Teixeira, Juliana H. Azambuja, Gabriela Debom, Francisco A. B. Del Pino, Roselia M. Spanevello & Elizandra Braganhol

  2. Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil

    Janaine M. Chassot & Letícia Cruz

  3. Departamento de Fisiologia e Farmacologia, Instituto de Biologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil

    Fátima T. Beira & Adriana Lourenço

  4. Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Rio Grande, Rio Grande, RS, Brazil

    Ana P. Horn

  5. Prédio 29; Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Capão do Leão, S/N, CEP 96.010-900, Caixa Postal 354, Pelotas, RS, Brazil

    Elizandra Braganhol

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  1. Elita F. da Silveira
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  2. Janaine M. Chassot
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  12. Elizandra Braganhol
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Correspondence to Elizandra Braganhol.

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da Silveira, E.F., Chassot, J.M., Teixeira, F.C. et al. Ketoprofen-loaded polymeric nanocapsules selectively inhibit cancer cell growth in vitro and in preclinical model of glioblastoma multiforme. Invest New Drugs 31, 1424–1435 (2013). https://doi.org/10.1007/s10637-013-0016-y

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