Fundamental advances in hydrogels for the development of the next generation of smart delivery systems as biopharmaceuticals.

Recent advances in developing and applying therapeutic peptides for anticancer, antimicrobial and immunomodulatory remedies have opened a new era in therapeutics. This development has resulted in the engineering of new biologics as part of a concerted effort by the pharmaceutical industry. Many alternative routes of administration and delivery vehicles, targeting better patient compliance and optimal therapeutic bioavailability, have emerged. However, the design of drug delivery systems to protect a range of unstable macromolecules, including peptides and proteins, from high temperatures, acidic environments, and enzymatic degradation remains a priority. Herein, we give chronological insights in the development of controlled-release drug delivery systems that occurred in the last 70 years or so. Subsequently, we summarise the key physicochemical characteristics of hydrogels contributing to the development of protective delivery systems concerning drug-targeted delivery in the chronospatial domain for biopharmaceuticals. Furthermore, we shed some light on promising hydrogels that can be utilised for systemic bioactive administration.