The Effect of Glutathione Incorporated as Chain Transfer Agent in Thermosensitive Hydrogels for Controlled Release of Therapeutic Proteins

Abstract

Hydrogels are important materials with properties that make them very useful in many medical applications, especially in drug delivery. Their facile formation under mild conditions of temperature and pH in aqueous conditions make them ideal for the encapsulation of biomolecules because they permit maintaining the structure and biological activity of proteins. This makes them especially useful in the controlled delivery of therapeutic proteins. Thermoresponsive hydrogels are attractive for the localized delivery of proteins. In particular, hydrogels made from N-isopropylacrylamide (NIPAAm) are important because polymers made from NIPAAm exhibit a transition temperature close to 32°C. This allows the formation of hydrogels that are very hydrophilic below the transition temperature (i.e. at room temperature) and transform into a collapsed, more solid-like state above the transition temperature. Thus, they can be made into lightly crosslinked materials that can be extruded through a small diameter needle but once they reach body temperature they solidify in place, making them attractive for localized drug delivery. One potential drawback of hydrogels based on NIPAAm is that the linear polymer chains do not degrade and, without proper measures, would bioaccumulate after the function of the hydrogel delivery system is accomplished. Chain transfer agents can help circumvent this problem. The addition of glutathione to polymerizing mixtures of NIPAAm and hydrolytically degradable crosslinkers result in thermoresponsive hydrogels with all the advantages that NIPAAm based materials provide. However, the resulting polymer chains are limited in molecular dimensions, such that they can be potentially removed by renal clearance. Besides, the addition of glutathione results in polymer chains that solubilize upon crosslink degradation even above the transition temperature of the polymer system. This approach will permit a wide range of applications of NIPAAm-based materials.