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

Abstract

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.