Hyperglycaemia is responsible for the major pathophysiological factor of diabetes-associated vascular endothelial injury, which mainly resulted from the disturbance of equilibrium between ROS generation and elimination. Eucalyptol was verified with exact anti-oxidation effects via stimulating the secretion of endogenous antioxidant enzymes against ROS. However, the volatility, instability and poor water solubility of eucalyptol limited its pharmacological activities in vivo. In this study, we developed carboxymethyl chitosan-coated lipid nanoparticles for eucalyptol (CMC/ELN) to facilitate oral administration. A thin lipid film dispersion method was used to prepare the ELN. After CMC coating, the diameter of ELN increased from 166 nm to 177 nm and charge reversal was observed. The nanocarrier enhanced the protective effects of eucalyptol both in the high level of glucose (HG)-damaged HUVECs and endothelial injury in type I diabetes mellitus (T1DM) rat model. Furthermore, the mechanism of eucalyptol on the promotion of Nrf2 and HO-1 and reduction on Keap1 expression have been verified both in the in vitro and in vivo model. Besides, the pharmacokinetics data were verified the promotion of the oral eucalyptol absorption by the nanocarrier. Taken together, we established an optimal oral delivery system that promoted oral administration of eucalyptol to exert protective effects on hyperglycaemia-induced vascular endothelial injury.
Keywords: Eucalyptol; carboxymethyl chitosan; endothelial injury; hyperglycaemia; lipid nanoparticles.