In vitro/in vivo evaluation of pH-sensitive Gambogenic acid loaded Zein nanoparticles with polydopamine coating

As one of the active pharmaceutical ingredients in Gamboge, Gambogenic acid (GNA) has shown diverse anti-tumor activities. To reduce the vascular irritation of GNA and improve its water solubility, tumor targeting, and bioavailability, GNA loaded Zein nanoparticles ( [email protected] NPs) was further coated by polydopamine (PDA) to develop [email protected] NPs by anti-solvent precipitation and surface modification. The results showed that particle size and Zeta potential of [email protected] NPs were about 310 nm and −40.8 mV with core–shell morphology confirmed by TEM. [email protected] NPs increased the water solubility of GNA by more than 700 times and showed pH-sensitive release behavior in PBS with pH 6.86. In vitro cytotoxicity tests showed that [email protected] NPs had higher inhibitory activity on HepG2 cells than free GNA, and their IC 50 were 1.59 μg/mL and 9.89 μg/mL, respectively. Additionally, the hemolysis and vascular irritation assay showed that [email protected] NPs had good cytocompatibility and reduced the irritation of GNA to blood vessels. Moreover, the in vivo pharmacokinetic experiments exhibited that the C max and AUC 0-t of [email protected] NPs were significantly improved approximately by 2.09-fold and 3.48-fold over that of GNA, respectively. In conclusion, [email protected] NPs solve many defects of GNA and provide a tumor-targeting drug delivery for GNA.