Background
Evodiamine has gained wide interests recently because of its antitumor activities. However, a superior bioavailability is required to achieve better efficacy due to its poor water solubility. The
Conclusions
The improved antitumor activities of evodiamine were attributed to the enhanced solubility and P-glycoprotein inhibition by HP-β-CD. These results are promising for the drug administration of EVO/HP-β-CD inclusion complexes to enhance the bioavailability of evodiamine in vivo.
Results
The EVO/HP-β-CD inclusion complexes were prepared by the kneading method and structurally characterized. P-glycoprotein ATPase assays firstly demonstrated that evodiamine was a substrate of P-glycoprotein, while HP-β-CD and EVO/HP-β-CD inclusion complexes inhibited P-glycoprotein by blocking P-glycoprotein ATPase activity. The EVO/HP-β-CD inclusion complexes may be a promising anticancer drug candidate without drug resistance. After given evodiamine or EVO/HP-β-CD inclusion complexes intervention, cell viability evaluation indicated that the half inhibition concentration of evodiamine and EVO/HP-β-CD inclusion complexes on HepG2 cells was 8.516 and 0.977 μM, respectively. The caspase-3 enzyme activity analysis and Annexin V/PI double-staining revealed that EVO/HP-β-CD inclusion complexes possessed better antitumor activities than evodiamine. Additionally, Hoechst 33258 staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay demonstrated that EVO/HP-β-CD inclusion complexes induced HepG2 cell apoptosis more effectively than evodiamine. Conclusions: The improved antitumor activities of evodiamine were attributed to the enhanced solubility and P-glycoprotein inhibition by HP-β-CD. These results are promising for the drug administration of EVO/HP-β-CD inclusion complexes to enhance the bioavailability of evodiamine in vivo.