RESUMO
Intraperitoneal insulin delivery has higher benefits than subcutaneous insulin administration but has limitations, including obstruction of the catheter used in delivery devices. To overcome these limitations this study assessed safety and efficacy of an alternative approach involving a new delivery device, named ExOlin®, allowing diffuse release of insulin in the extraperitoneal site. The aim of this study is to validate both safety and efficacy of insulin delivery in extraperitoneal using ExOlin® device. Safety of the ExOlin® device implantation in the extraperitoneal site was investigated over a 3-month period in Wistar rat and landrace swine models before comparing efficacy pharmacokinetics and hepatic first-pass metabolism of insulin after focal delivery using a catheter or diffuse release via ExOlin® device in extraperitoneal. Implantation in rat and swine models demonstrated good integration of the device, validating the safety of the extraperitoneal site. In diabetic rats, direct insulin administration at the extraperitoneal showed an efficacy comparable to intraperitoneal and statistically significantly higher than subcutaneous route as shown by 23% lower AUC calculated from glycaemia profile. Diffuse extraperitoneal delivery of insulin via ExOlin® device in diabetic rats exhibited better efficacy than the subcutaneous route with up to six-fold lower peripheral insulin and higher hepatic first-pass than with intraperitoneal injection. Similar results were confirmed in the swine model after injecting insulin lispro via the device at the extraperitoneal site. In conclusion, diffuse administration of insulin at the extraperitoneal site via ExOlin® device is a new promising approach to physiologically treating type 1 diabetes. It can therefore be considered as a promising alternative to intraperitoneal route.