Research Topic

Innovative Chemical Crosslinking Strategies to Develop Smart Hydrogels for Protein Delivery

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Polymeric hydrogels represent a versatile tool that can be customized according to the type of polymer, crosslinking, and strategy of fabrication. Hydrogels can be used as delivery carriers due to their inherent set of physical and chemical properties that are ideal for the loading and release of many drugs ...

Polymeric hydrogels represent a versatile tool that can be customized according to the type of polymer, crosslinking, and strategy of fabrication. Hydrogels can be used as delivery carriers due to their inherent set of physical and chemical properties that are ideal for the loading and release of many drugs as well as macromolecules. Specifically, in the field of protein delivery, hydrogels have been investigated as dosage forms that can act as depot systems for the sustained release of therapeutic proteins. Several hydrogel types including pH-sensitive and interpenetrating stimuli-responsive matrices have been proposed as innovative solutions to promote targeted and sustained delivery of proteins. Despite many efforts, only a few formulations have reached preclinical and clinical evaluation suggesting that this field of study requires further investigation to obtain the next generation of dosage forms for efficient protein delivery.

The biological activity of proteins strictly depends on their stability in physiological conditions, which indirectly regulates the therapeutic active dose and the corresponding pharmacological effect. Therefore, there is a critical need to design suitable polymeric carriers to promote the release of proteins while protecting them from enzymatic degradation or hydrolysis. Polymeric drug delivery carriers can be used as platforms to enhance the therapeutic efficacy of these bioactive molecules. Specifically, the degree of crosslinking, porosity, degradability, and rheological properties can be modified to modulate the release of these therapeutic macromolecules. However, further improvements in this field are required to investigate how the polymer crosslinking process can be controlled to avoid protein denaturation during the loading step. Similarly, clinically translatable protein delivery systems need to be identified by taking into consideration not only their efficacy in vitro but also their efficacy and safety when in contact with biological systems in vivo.

The scope of this Research Topic is to highlight recent advancement in the chemical design of polymeric hydrogels to promote controlled and targeted release of proteins. This Research Topic is open to both Original Research and Review articles that discuss or investigate one or more of the following key points:

• Alternative chemical crosslinking strategies aimed to modulate hydrogel properties to control the release of therapeutic proteins.
• Innovative polymeric hydrogel fabrication strategies to modulate protein release. Examples include, but are not limited to, double network hydrogels, cryogels, and in situ forming hydrogels.
• Characterization of polymeric hydrogels physical and biological properties to create safe injectable delivery systems for protein administration.
• Alternative and smart approaches for the loading and delivery of proteins from hydrogels.
• Production of hydrogel-based formulations for protein delivery with applicability in pre-clinical and clinical settings for regenerative medicine.


Keywords: Protein release, cryogels, injectable hydrogel, pH-sensitive hydrogels, sustained delivery


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