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

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.

Preclinical evaluation of Trichilia catigua extracts on the central nervous system of mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Trichilia catigua preparations have been popularly used in Brazil as a tonic for the treatment of fatigue, stress, impotence, and deficiency of memory. The aim of the present study was to investigate the possible antidepressant, anxiolytic, motor and cognitive effects of the crude extract (CE) or ethyl-acetate fraction (EAF) of Trichilia catigua. Analyses of the total phenolics and total tannins content, as well as the in vitro antioxidant activity of CE and EAF were also performed. MATERIALS AND METHODS: CE (200-800 mg/kg) and EAF (100-400mg/kg) were orally administered to mice and 1h later the behavioral tests were performed. The free radical scavenging activity was measured by using 2,2-diphenyl-1-picryl-hydrazyl (DPPH) method. RESULTS: Single administration of CE (200-400 mg/kg) or EAF (100-400 mg/kg) did not change the behavior of the animals submitted to the elevated plus maze or their locomotor activity in the open field test. An antidepressant-like effect was detected with EAF (400 mg/kg) after acute administration. Both CE (800 mg/kg) and EAF (200 and 400 mg/kg), improve memory in mice as measured by an increased latency in the step-down inhibitory avoidance test. The EAF presented higher total phenolics and total tannins as compared to CE as well as it exhibited the best antioxidant activity. CONCLUSIONS: The present results showed an in vitro antioxidant activity for EAF and suggested that it may be useful for cognitive improvement. It is possible that both functional and chemical activities are related.