In our previously studies, we confirmed that ergosterol could ameliorate diabetic nephropathy by suppressing the proliferation of mesangial cells and the accumulation of extracellular matrix (ECM). However, the therapeutic application of ergosterol may be confined due to poor aqueous solubility and low oral bioavailability. We aim to prepare ergosterol-loaded nanostructured lipid carriers (ERG-NLCs) to enhance the solubility and oral bioavailability of ergosterol. ERG-NLCs were prepared using glyceryl monostearate and decanoyl/octanoyl-glycerides by hot emulsification-ultrasonication method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) analysis, entrapment efficiency (EE), and drug loading (DL) capacity studies. The prepared ERG-NLCs were spherical, with particle size of 81.39 nm and negative zeta potential of 30.77 mV. Ergosterol was successfully encapsulated in NLCs with a high EE of 92.95% and a DL capacity of 6.51%. In pharmacokinetic study, Cmax and AUC0-∞ of ergosterol in ERG-NLCs were obviously enhanced, and the relative oral bioavailability of ERG-NLCs was 277.56% higher than that of raw ergosterol. Moreover, the in vitro pharmacodynamic study indicated that ERG-NLCs inhibited high-glucose-stimulated mesangial cells over proliferation and ECM accumulation more effectively compared to raw ergosterol. In conclusion, the validated ERG-NLCs showed that NLCs mediated delivery could be used as potential vehicle to enhance solubility, oral bioavailability and therapeutic efficacy of ergosterol.
Keywords: Diabetic nephropathy; Ergosterol; Nanostructured lipid carrier(s).