In Vivo Release of Insulin from NPH/Pluronic F127 in Streptozotocin-Induced Diabetic Rats

Nova Southeastern University, Davie, Florida, USA

Objective: The purpose of this study is to test basal insulin formulations (NPH/Pluronic F127) to streptozotocin-induced diabetic rats. Background: NPH insulin exhibits peak at 4-6 hours followed by decline of insulin action. Insulin release from NPH is facilitated by the tissue enzyme activity degrading the protamine moiety that stabilizes NPH. Therefore, an in situ hydrogel-forming thermosensitive Pluronic F127 was utilized to attenuate protamine degradation in NPH, thereby reducing the burst release and extend its duration of action. This was confirmed by the previous insulin release studies in vitro. Methods: Male Wistar rats were given appropriate intraperitoneal dose of streptozotocin. Plasma glucose was monitored for one week. Insulin formulation (4U/kg) or saline was given to a group of 6 animals. Pluronic F127 concentration was varied from 15 % (w/w) to 25 % (w/w). Plasma glucose concentrations for each group were monitored over 24h. Results: The NPH insulin SC dose of 4U/kg resulted in the minimum plasma glucose level of less than 50 mg/dL, followed by a rapid rise over the course of 12-16 hours. The NPH entrapped in 25% Pluronic F127 exhibited a peak-less glucose dynamics over 24h. Conclusion: Insulin release and glucose dynamics by NPH in diabetic rats were altered by the presence of a hydrogel barrier, which may have attenuated the tissue enzyme activity that facilitates NPH action. This system can potentially benefit diabetic patients by providing native human insulin once daily. Grants: The work was supported in part by Health Profession Division Grant, Nova Southeastern University.