Development and evaluation of novel hydrogel for preventing postoperative pancreatic fistula

Abstract

Pancreatic fistula is a complication that frequently occurs after pancreatic surgery. Although various attempts have been made to prevent pancreatic fistula after pancreatic surgery, no effective methods have been developed thus far. In this study, to prevent the pancreatic fistula, we attempted to prepare the hydrogels consisting of two types of polyvinyl alcohol (PVAs), Poval® and Exceval® by the freezing–thawing (F/T) method. As the concentration and the number of F/T cycles increased, it was revealed that the swelling degree tended to decrease, and tensile strength tended to increase. Especially, Exceval® formed more robust hydrogels than that of Poval® hydrogel prepared by the same conditions. Furthermore, the release behavior of tartrazine from 10% Exceval® hydrogels differed depending on the number of F/T cycles. It was also revealed that the diffusion pattern of the drug in the hydrogel differed along with the release, and the entire amount of tartrazine in the hydrogel was released by 120 min. As nafamostat mesylate was loaded, in vivo study, Pancreatic enzyme values were obtained after 48 h, which allowed comparison of the preventive effects against pancreatic fistula between the untreated group, the Exceval® hydrogel group, and nafamostat mesylate-containing Exceval®-applied group. Furthermore, there was a significant difference between the untreated group and the hydrogel-applied group. Besides, PVA hydrogels prepared by the F/T method could probably absorb pancreatic enzymes. This study found that Exceval® hydrogel prepared by the F/T method was considered a novel hydrogel formulation to prevent pancreatic fistula.