Nanoemulsion as a novel carrier system for improvement of betulinic acid oral bioavailability and hepatoprotective activity

Abstract

Betulinic acid (BA) is a potent bioactive compound and well known for its therapeutic activity. However, its efficacy is restricted due to low solubility as well as poor bioavailability. The aim of the study was to develop a BA loaded nanoemulsions for enhanced bioavailability and hepatoprotective activity. The optimized nanoemulsion (BA-NE1) was composed of olive oil, aqueous phase and Smix [surfactant (labrasol) and co-surfactant (plurol isostearate)] in an appropriate ratio of 20:25:55% w/w respectively. BA-NE1 was prepared by spontaneous nano-emulsification method. The BA-NE1 was characterized through different parameters including droplet size, zeta potential, refractive index, transmission electron microscopy, UV-spectrophotometry, Fourier transform infrared spectroscopy and stability study. The appropriate droplet size (150.3±0.56nm) and zeta potential (−10.2±0.11mV) were observed for BA-NE1. The improved pharmacokinetics parameters Cmax (96.29±1.96ngmL−1), AUC0-t∞ (2540.35±278.31nghmL−1), Tmax (12.32±0.05h), elimination half-life (11.35±3.20h) and relative bioavailability (440.48%F) were significantly achieved with BA-NE1 compared to BA. The BA-NE1 significantly restored the levels of serum hepatic markers and hepatic antioxidant enzymes with respect to CCl4-intoxicated groups (⁎⁎p<0.05 and ⁎⁎⁎p<0.01). Therefore, the present study suggests that BA loaded nanoemulsion may enhance the hepatoprotective activity which may be due to its increased solubility as well as improved oral bioavailability.