Effective Platform for Enhancing the Bioavailability and Anti-Cancer Efficacy of Norcantharidin: Nanoemulsion Hybrid Lipid Carriers

Abstract

Novel antitumor drugs and nano-delivery systems for treating liver cancer are becoming a research hotspot, given that the incidence and mortality rates of liver cancer are high. Herein, nanoemulsion hybrid lipid carriers containing norcantharidin (Nor) (NNHLCs) were first prepared by loading water-in-oil nanoemulsions into hybrid solid lipids using nanoemulsion-thin film ultrasonic dispersion method. The in vitro and in vivo kinetic features were determined by in situ unidirectional perfusion and plasma concentration-time curve method, respectively. The activity of NNHLCs against liver cancer HepG2 cells was determined by evaluating in vitro cytotoxicity, clone formation, apoptosis, and cell cycle experiments. Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) results indicated that Nor exists in NNHLCs in an amorphous state with good encapsulation in the lipid matrix. The absorptive constants and permeabilities of NNHLCs were significantly increased compared with Nor. The relative bioavailability of NNHLCs to Nor was 207.68%. NNHLCs could inhibit the viability and proliferation of HepG2 cells and promote apoptosis. Thus, nanoemulsion hybrid lipid carriers may provide a new option for the efficient delivery of chemotherapeutic drugs.