Local application of triamcinolone acetonide-conjugated chitosan membrane to prevent benign biliary stricture.

ABSTRACT

Benign biliary stricture (BBS) is the proliferation of fibrous tissue of the biliary tract caused by the biliary operation, bile duct stones, cholangitis, trauma, and other etiologies due to scar contracture. Recent therapeutic strategies to suppress stenosis are insufficient. Here, we developed a sustained-release membrane (SM) of triamcinolone acetonide (TA) with N-succinyl hydroxypropyl chitosan (TASM) for inhibiting fibroblast proliferation in vitro and bile duct hyperplasia in the rabbit model for benign biliary stricture formation. The TASM were successfully placed in 45 of 50 rabbits. Evaluation of subcutaneous stimulation and acute liver injury confirms the safety of TASM in vivo. Compared to the control group, the TASM can significantly inhibit the proliferation of scar muscle fibroblasts in vitro. ELISA and immunofluorescence showed TASM could increase bFGF level and inhibit expression of TGFß1 and αSMA. Cholangiographic and histologic examinations demonstrated significantly decreased tissue hyperplasia in the TASM groups compared with the model group. The immunohistochemical staining showed that TASM could reduce the level of cytokine-induced scars and inhibit the proliferation of myofibroblasts. Taken together, the chitosan membrane chemically conjugated with TA can effectively inhibit the benign biliary stricture. Further clinical usage of this membrane may effectively reduce the occurrence of benign biliary stricture.