Suna Choi1, Sung Wan Kim. 1. Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112-5820, USA.
Abstract
PURPOSE: The purpose of this study was to design sustained release system which provides basal insulin release over a week by one injection in diabetic animals. For an effective injectable formulation and controlled release of insulin, a water soluble biodegradable triblock copolymer of PLGA-PEG-PLGA was used. METHODS: For in vitro release, samples were analyzed by reversed-phase high performance liquid chromatography. Animal studies using ZDF rats have been conducted to demonstrate the bioactivity of the released insulin. Insulin formulation was injected subcutaneously. At designated times, the blood glucose levels and insulin levels of the ZDF rats were measured. RESULTS: The in vitro release of zinc-complexed insulin showed no initial burst and demonstrated constant release rate with the duration of 14 days. Constant steady state plasma levels of exogenous insulin were detected for nearly two weeks indicating constant rate of insulin release in vivo upon single subcutaneous injection. CONCLUSIONS: We conclude that it is feasible to achieve basal insulin levels over a week by a single injection of ReGel formulation. This will provide various advantages, including depot formation without surgery, easy sterilization, straightforward drug loading, simple dose adjustment, system biocompatibility with no inflammatory reaction, and no requirement of using organic solvents.
PURPOSE: The purpose of this study was to design sustained release system which provides basal insulin release over a week by one injection in diabetic animals. For an effective injectable formulation and controlled release of insulin, a water soluble biodegradable triblock copolymer of PLGA-PEG-PLGA was used. METHODS: For in vitro release, samples were analyzed by reversed-phase high performance liquid chromatography. Animal studies using ZDFrats have been conducted to demonstrate the bioactivity of the released insulin. Insulin formulation was injected subcutaneously. At designated times, the blood glucose levels and insulin levels of the ZDFrats were measured. RESULTS: The in vitro release of zinc-complexed insulin showed no initial burst and demonstrated constant release rate with the duration of 14 days. Constant steady state plasma levels of exogenous insulin were detected for nearly two weeks indicating constant rate of insulin release in vivo upon single subcutaneous injection. CONCLUSIONS: We conclude that it is feasible to achieve basal insulin levels over a week by a single injection of ReGel formulation. This will provide various advantages, including depot formation without surgery, easy sterilization, straightforward drug loading, simple dose adjustment, system biocompatibility with no inflammatory reaction, and no requirement of using organic solvents.
Authors: G M Zentner; R Rathi; C Shih; J C McRea; M H Seo; H Oh; B G Rhee; J Mestecky; Z Moldoveanu; M Morgan; S Weitman Journal: J Control Release Date: 2001-05-14 Impact factor: 9.776