Smart Hydrogels for Advanced Drug Delivery Systems

Since the last few decades, the development of smart hydrogels, which can respond to stimuli and adapt their responses based on external cues from their environments, has become a thriving research frontier in the biomedical engineering field. Nowadays, drug delivery systems have received great attention and smart hydrogels can be potentially used in these systems due to their high stability, physicochemical properties, and biocompatibility. Smart hydrogels can change their hydrophilicity, swelling ability, physical properties, and molecules permeability, influenced by external stimuli such as pH, temperature, electrical and magnetic fields, light, and the biomolecules’ concentration, thus resulting in the controlled release of the loaded drugs. Herein, this review encompasses the latest investigations in the field of stimuli-responsive drug-loaded hydrogels and our contribution to this matter.

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About this article: Bordbar-Khiabani, A., Gasik, M. Smart Hydrogels for Advanced Drug Delivery Systems. Int. J. Mol. Sci. 2022, 23, 3665. https://doi.org/10.3390/ijms23073665

Conclusions, Challenges, and Future Directions
The introduction of stimulus-responsive effects can enhance the functionality and increase the range of applications of hydrogels in biomedical engineering. Smart hydrogels as an emerging class of material responding to external triggers, such as pH, temperature, electrical and magnetic fields, light, and concentration of biomolecules, can release the drug cargo at specific locations with controllable kinetics. Based on the last five years’ studies, the main future direction is to improve the properties of the currently developed smart hydrogels and provide them with novel, sophisticated features. In the near future, research will move toward the synthesis of programmable smart hydrogels that are capable of responding to the complex multi-stimulus and integrating multiple therapies. They are likely to have an exciting future, while some challenges are facing this field. Up to now, various smart hydrogels have been developed and introduced, but the commercialization of smart hydrogels as drug delivery systems is not convincing; only a few cases have entered into clinical use, including Jelmyto^® (UGN-101) as a TRH that was lunched by UroGen Pharma and received Food and Drug Administration (FDA) approval in April 2020 [105]. Indeed, given the recent advances in the pharmaceutical industry, there are still no clear legal regulations and standards for the use of smart drug-loaded hydrogels in therapeutic activities. Moreover, much progress needs to be made concerning in vivo release by modeling the release profiles before commercializing them. Finally, the field of smart hydrogels is in its infancy and its importance in designing efficient delivery systems has become clear to everyone and can create many opportunities for 21st century medicine. The next generations of smart hydrogels will most likely focus on gene-loaded hydrogels with integrated sensors to treat genetic abnormalities. Another possible research area will be pathogen-responsive hydrogels for local infection treatments. Recently, the “Gels4Bac” project has been funded by the European Research Council (ERC) and will focus on the selectively and local release of antimicrobial vesicles in the presence of specific pathogen stimuli.