Tripodal amphiphilic pseudopeptidic nano-vesicles as p-coumaric acid delivery systems for brain cancer cells

Abstract

Nano-vesicles based on tripodal amphiphilic pseudopeptides (TRAP) are prepared as carriers for p-coumaric acid delivery. Loaded nano-vesicles are obtained by both thin film hydration and ethanol injection methods with positive Z-potential (ZP) values. The last technique renders lower particle sizes and excellent polydispersity index (PDI), with average values of 130 nm and 0.123 respectively, although the drug loading obtained after ultracentrifugation is lower. In-vitro release experiments, including the use of different external stimuli like pH and proteolytic enzymes provide interesting results. The prepared nano-vesicles are tested on normal cells (VERO) displaying a high safety profile scoring with a 50% inhibitory concentration (IC 50) of 1822 µg/mL. A 40-times increase in the in-vitro cytotoxic effect of p -coumaric acid (p -CA) on Glioma GL261 brain cancer cells, from IC 50 1082 µg/mL to 29 µg/mL, is observed using the loaded pseudopeptide nano-vesicles. 1 H NMR studies reveal that the drug is mainly located inside the nano-particle bilayer. Transmembrane carboxyfluoresceine (CF) studies reveal that the amphiphilic compound does not provide a significant membrane fluidification. Experimental data suggest that the observed biological activity can be associated to an enhanced permeability and retention effect (EPR). The present results highlight the potential of such nano-vesicles as potent p -coumaric acid carriers for brain cancer therapy.