Synthesis of redox - responsive hydrogels for controlled release of therapeutic agents

Abstract

In recent years, hydrogels have attracted great attention for various biomedical applications ranging from chemical and biological sensing, delivery of therapeutic agents to tissue engineering. Reason for utilization of hydrogels for the aforementioned applications stems from our ability to design them with desirable physical and chemical characteristics. Properties like their high swelling in aqueous media, controlled biodegradation, biocompatibility, tailorable elasticity and porosity are among a few of such attributes. Tailoring the release characteristics of encapsulated therapeutic agents is crucial for many biomedical applications. To achieve a control over release profile, hydrogels with well-defined network connectivity are becoming popular due to their homogeneous inner structure. Crosslinking of well-defined multi-arm polymers with high efficiency provides a viable synthetic methodology to obtain hydrogels with better control over network structure. In this thesis work, we report the fabrication of well-defined hydrogels by reacting two different multi-arm polymers with complementary reactive groups in a fast and effective manner under environmentally benign conditions. Hydrogels were fabricated by crosslinking of two different tetra-arm poly(ethylene glycol) based polymers, one containing pyridyl-disulfide and the other bearing thiol groups, in phosphate saline buffer, with gel conversions between 89-93%. Efficiency of the crosslinking process based on end group consumption analysis suggested chain coupling as high as 90-95%. Rheological and morphological characterizations revealed stable hydrogels with porous structures. It was demonstrated that the disulfide groups within the hydrogels undergo degradation in the presence of thiol-containing agents such as glutathione and DTT, to release the encapsulated therapeutic agents in a controlled or ondemand fashion.