Insights into current directions of protein and peptide-based hydrogel drug delivery systems for inflammation

An immune system responds to pathogens, toxic compounds, or certain physiological conditions which lead to inflammation. However, uncontrolled and excessive inflammation is associated with a variety of severe chronic conditions including intestinal disorders, cancer, diabetes, and myocardial infarction. The development of anti-inflammatory therapies to treat and manage relevant chronic diseases has resulted from a better understanding of inflammation. However, clinical outcomes vary among patients and serious adverse effects are often observed. Furthermore, clinical anti-inflammatory therapeutics have some limitations due to their insolubility in water, low bioavailability, and poor accessibility to subcellular compartments. To address these challenges, the drug delivery system specific to inflammation offers significant potential. A hydrogel is attractive as a drug delivery platform because of its outstanding characteristics, including swellability, biocompatibility, controlled degradation, and sustained drug release. Hydrogels have been widely used in biomedical applications for several reasons, using diverse polymers of synthetic and natural origin. The design of hydrogels relies heavily on proteins and peptides because proteins are the fundamental macromolecules in living organisms for biochemical, mechanical, and structural functions. Therefore, they provide us with a wide range of structural building blocks for the formation of various types of biomaterials, including hydrogels. Since natural proteins and peptides are biocompatible and biodegradable, they have features advantageous for their use as the building blocks of hydrogels for biomedical applications. This review aims to focus on hydrogels derived from protein and peptide-based systems and highlights recent trends in the use of protein and peptide-based hydrogels as drug delivery systems for inflammation.