4.5 Article

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

Journal

INVESTIGATIONAL NEW DRUGS
Volume 31, Issue 6, Pages 1424-1435

Publisher

SPRINGER
DOI: 10.1007/s10637-013-0016-y

Keywords

Gliomas; Ketoprofen; Polymeric nanocapsules; Drug delivery

Funding

  1. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
  2. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
  3. Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS) [10/0286-2]
  4. CAPES Master fellowship

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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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