Enzyme Responsive Delivery of Engineered Antibody Fragments

Therapeutic proteins including antibodies (or antibody fragments), cytokines and growth factors are a rapidly expanding drug class in clinical use for treatment of various diseases. However, in vivo protein delivery remains a challenge because of their instability and short half-life, often resulting in poor drug bioavailability at disease sites. Hydrogels are extensively studied for the localized and sustained delivery of proteins due to their excellent biocompatibility, tunable biodegradability and ability to mimic native extracellular matrix (ECM). For instance, injectable hydrogels as drug delivery system (DDS) can be applied to deliver these therapeutic proteins and to increase their retention time in the joint space resulting in enhanced osteoarthritis (OA) treatment effects. To improve the release kinetics of proteins from hydrogels the complementary use of both chemical and genetic methods, by engineering proteins with intrinsic features such as a proteinase cleavage site, reactive handle for bioconjugation, and affinity domain for interaction with materials, may provide a new concept in designing a controlled release system for protein delivery.