Established new compound IMB16-4 self-emulsifying drug delivery systems for increasing oral bioavailability and enhancing anti-hepatic fibrosis effect.

Liver fibrosis results from the chronic liver injury and no specific medical therapy is approved so far. Recently, new compound, N-(3,4,5-trichlorophenyl) - 2 (3-nitrobenzenesulfonamido) benzamide, referred to as IMB16-4, was developed to resist liver fibrosis. However, IMB16-4 displays poor aqueous solubility and poor oral bioavailability. To increase the dissolution rate, improve the oral bioavailability and enhance the anti-hepatic fibrosis action of IMB16-4, IMB16-4 self-emulsifying drug delivery systems (SEDDS) with negative charge or positive charge were prepared using simple stirring, respectively. Their stability, oral bioavailability and anti-liver fibrosis effect were evaluated. The results showed IMB16-4 SEDDS in simulated gastric juice were nearly spherical with the diameter of 100～200 nm and possessed good stability in 30 days. The oral bioavailability of IMB16-4 SEDDS with negative charge and positive charge were increased to 33 folds and 58 folds compared with that of pure IMB16-4, respectively. In bile duct ligation (BDL) rats, IMB16-4 SEDDS attenuated the degree of liver damage and decreased collagen accumulation. In addition, IMB16-4 SEDDS with negative charge easily accumulated in the liver and alleviated hepatic fibrosis by TGF-β/Smad signaling. These findings indicate that IMB16- 4 SEDDS may be a potential therapy for the treatment of liver fibrosis.