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

• Published in: Materials today chemistry 2023-01, Vol.27, p.101266, Article 101266
• Main Authors: Lotfallah, A.H., Andreu, J.J., Hathout, R.M., Kassem, D.H., Ibrahim, S.S., Altava, B., García-Verdugo, E., Luis, S.V.
• Format: Article
• Language: English
• Subjects: Brain cancer; Drug delivery; Nanovesicles; Pseudopeptide; Self-assembly
• ISSN: 2468-5194; 2468-5194
• DOI: 10.1016/j.mtchem.2022.101266

Nanovesicles based on tripodal amphiphilic pseudopeptides are prepared as carriers for p-coumaric acid (p-CA) delivery. Loaded nanovesicles are obtained by both thin film hydration and ethanol injection methods with positive Z-potential values. The last technique renders lower particle sizes and excellent polydispersity index, 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 such as pH and proteolytic enzymes, provide interesting results. The prepared nanovesicles are tested on normal cells (VERO), displaying a high safety profile scoring with a 50% inhibitory concentration (IC50) of 1,822 μg/mL. A 40-times increase in the in vitro cytotoxic effect of p-CA on Glioma GL261 brain cancer cells, from IC50 1,082 μg/mL to 29 μg/mL, is observed using the loaded pseudopeptide nanovesicles. 1H NMR studies reveal that the drug is mainly located inside the nanoparticle bilayer. Transmembrane carboxyfluorescein 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. The present results highlight the potential of such nanovesicles as potent p-CA carriers for brain cancer therapy. [Display omitted] •Nanovesicles based on tripodal amphiphilic pseudopeptide are prepared as carriers for p-coumaric acid delivery.•Nanovesicles with average values of particle sizes of 130 nm and polydispersity index of 0.123 are obtained.•A high safety profile on normal cells of tripodal amphiphilic pseudopeptide nanovesicles is observed.•In vitro cytotoxic effect of p-coumaric acid increases 40 times when loaded on nanovesicles.•In vitro release studies in the presence of thermolysin facilitated a faster drug release.