In Vivo Study of a Polymeric Glucose-Sensitive Insulin Delivery System Using a Rat Model

Abstract

This study assesses the feasibility of an intraperitoneal (IP) implantable closed-loop insulin delivery device in rats, that delivers insulin via a glucose-sensitive material such that blood glucose (BG) levels are adjusted automatically to within normal tolerances. A gateway layer of this gel governs the output of insulin from an insulin reservoir device for IP implant. The performance of the system was compared over time in diabetic rats with a control system using oral glucose challenges and daily assessments of BG and body weight. The automated response of the active system was quantified using IP multiple dose injection (MDI) results in the same rat model. Successful control was found for the device containing active gel when assessed daily and when challenged with large glucose doses. This was not found when comparing an inactive gel analog as a control. The regimen was quantified by comparison with the informative MDI study. The device was well tolerated and might operate to further advantage when vascular omentum grows into the perforated front of the device. The successful device must have been outputting approximately 0.5 U/kg/h basal with 2 U/kg boosts in order to match the demand of the challenges. However, the device eventually exhausts and a refill mechanism needs to be devised in future models.