Ergosterol-loaded poly（lactide-co-glycolide） nanoparticles with enhanced in vitro antitumor activity and oral bioavailability

Aim： Ergosterol is a plant sterol with anti-tumor and anti-angiogenic activities, but is poorly soluble. In this study, we attempted to enhance its anti-tumor action and oral bioavailability via poly（lactide-co-glycolide） （PLGA） nanoparticle encapsulation. Methods： Ergosterol-loaded PLGA nanoparticles （NPs/Erg） were prepared using the emulsion/solvent evaporation technique. Their physicochemical properties were characterized, and their cytotoxicity against human cancer cell lines was evaluated with MTT assay. The pharmacokinetics and tissue distribution of NPs/Erg were investigated in rats and mice, respectively. Results： NPs/Erg were spherical in shape with a particle size of 156.9＋4.8 nm and a Zeta potential of -19.27_＋1.13 mY, and had acceptable encapsulation efficiency and loading capacity. NPs/Erg exerted much stronger cytotoxicity against human cancer cells than the free ergosterol, and showed significantly reduced ICso values （14.69＋0.48 pg/mL in glioma U251 cells; 9.43＋0.52 pg/mL in breast cancer MCF-7 cells; 4.70＋_0.41 pg/mL in hepatoma HepG2 cells）. After oral administration of a single dose in rats, NPs/Erg displayed a prolonged plasma circulation with a 4.9-fold increase of oral bioavailability compared with the free ergosterol. After mice received NPs/Erg, the ergosterol in NPs/Erg was rapidly distributed in stomach, kidneys, liver, brain, spleen, and virtually non-existent in heart and lungs. The presence of NPs/Erg in brain was particularly improved compared with the free ergosterol. Conclusion： The PLGA nanoparticles serve as a promising carrier for the poorly soluble ergosterol and significantly improve its bioavailability, biodistribution and in vitro anti-tumor activities.