In‐Situ Gelling Thermosensitive Hydrogels for Protein Delivery Applications

Hydrogels cover an extremely broad variety of medical, biological and pharmaceutical applications, chemical composition and gelation mechanisms. They range from chemically to physically crosslinked networks of synthetic or natural polymers, can be manufactured into materials of different shapes and dimensions (from macroscopic depots to nanogels/nanofibers) and formulated in such a way that they become degradable in a specific controllable manner. Research on the controlled release of proteins and peptides covers a sizeable portion of the work on hydrogels. Pharmaceutical proteins have increased remarkably in number and frequency of use. However, their delicate three-dimensional structure is a major limitation to the use of pharmaceutical proteins, as they suffer from poor stability, due to proteolytic and chemical degradation as well as physical unfolding and aggregation. This instability leads to loss of activity and often elicits an immune response. Injectable hydrogel-based controlled release delivery systems are among the approaches implemented to enhance protein’s pharmacokinetic and pharmacodynamic properties. Hydrogels are crosslinked networks of hydrophilic polymers capable of retaining large amounts of water yet remaining insoluble and maintaining their three-dimensional structure. They can entrap, protect from degradation and slowly release proteins in a controlled fashion in order to maintain a therapeutic effective concentration of the protein drug in the surrounding tissues or in the circulation over an extended period of time. This chapter is intended as a small cross section of the multidisciplinary and exciting research ongoing in the area of hydrogels for protein delivery, with particular emphasis on in-situ gelling thermosensitive hydrogels.