Loading and mobility of spin-labeled insulin in physiologically responsive complexation hydrogels intended for oral administration

摘要

Poly(methacrylic acid-g-ethylene glycol) copolymers are pH-responsive complexation hydrogels that have shown promise in in vitro and in vivo results as oral insulin delivery carriers. With the aim of gaining more detailed insight into their performance to further improve the carriers, we spin-labeled insulin and used electron spin resonance (ESR) spectroscopy to follow the loading of the spin-labeled insulin into the copolymer microparticles. A flow through system was developed to monitor continuously and non-invasively the dynamics of the spin-labeled insulin and its surrounding microviscosity during release. Using these methods, the loading efficiency of insulin was determined and was found to match previous HPLC measurements. Additionally, the protein- friendly nature of the hydrogels was demonstrated. The monitoring of the dynamics during flow through provided a rationalization for the unwanted initial burst release in an acidic environment. These studies will aid in the optimization of the system, and will be a basis for subsequent in vivo ESR investigations. (c) 2005 Elsevier B.V. All rights reserved.