Fast Absorbent and Highly Bioorthogonal Hydrogels Developed by IEDDA Click Reaction for Drug Delivery Application

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Injectable hydrogels offer minimally invasive drug delivery solutions.
• Hyaluronic acid (HA)-based materials are known for their biocompatibility.
• Click chemistry provides efficient and specific methods for hydrogel formation.

Purpose of the Study:

• To engineer highly biocompatible and fast-absorbing injectable hydrogels.
• To utilize the inverse electron demand Diels−Alder (IEDDA) click reaction for hydrogel network formation.
• To investigate the tunability of hydrogel properties (porosity, gelation, mechanical strength, swelling) for drug delivery applications.

Main Methods:

• Functionalization of hyaluronic acid with norbornene (HA-Nb).
• Synthesis of a polyethylene glycol cross-linker with tetrazine groups (PEG-DTz).
• Formation of hydrogels via the IEDDA click reaction between HA-Nb and PEG-DTz.
• Characterization of hydrogel properties including porosity, gelation time, mechanical strength, swelling ratio, and drug encapsulation/release.
• Cytotoxicity assessment using HEK-293 cells.

Main Results:

• Rapidly gelling (<100 s) and highly porous injectable hydrogels were successfully fabricated.
• Tunable hydrogel properties were achieved by varying the HA-Nb to PEG-DTz molar ratio.
• Hydrogels exhibited rapid swelling, high swelling ratios, and efficient encapsulation (~99%) of curcumin.
• Curcumin release demonstrated a temporal release pattern.
• No cytotoxicity was observed for the components or the resulting hydrogels in HEK-293 cells.

Conclusions:

• Injectable, biocompatible, and fast-absorbing hydrogels were developed using HA-Nb and PEG-DTz via IEDDA click chemistry.
• The tunable porosity and rapid absorption make these hydrogels suitable for injectable drug delivery.
• These novel hydrogels hold promise as effective drug carriers with excellent biocompatibility.