New IMB16-4 Hot-Melt Extrusion Preparation Improved Oral Bioavailability and Enhanced Anti-Cholestatic Effect on Rats.

ABSTRACT:

Background

Cholestasis is challenging to treat due to lacked effective drugs. N-(3,4,5-trichlorophenyl)-2 (3-nitrobenzenesulfonamido) benzamide, abbreviated as IMB16-4, which may be effective for the treatment of cholestasis. However, its poor solubility and bioavailability seriously obstruct the research programs.

Methods

A hot-melt extrusion (HME) preparation was first applied to increase the bioavailability of IMB16-4, the oral bioavailability, anti-cholestatic effect and vitro cytotoxicity of IMB16-4 and IMB16-4-HME were evaluated. Meanwhile, the molecular docking and qRT-PCR were used to validate the mechanism behind.

Results

The oral bioavailability of IMB16-4-HME improved 65-fold compared with that of pure IMB16-4. Pharmacodynamics results demonstrated that IMB

SUBMITTER: Li Y 

PROVIDER: S-EPMC9985389 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature