Light-activatable prodrugs based on hyaluronic acid biomaterials

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Hyaluronan (HA) is a key extracellular matrix polysaccharide.
• Developing light-sensitive hydrogels is crucial for controlled therapeutic delivery.
• Existing hydrogel systems often lack precise light-triggered degradation and release.

Purpose of the Study:

• To create photosensitive, in situ cross-linked hyaluronan (HA) hydrogels.
• To engineer light-triggered drug-releasing hydrogel prodrugs using HA.
• To investigate the controlled release of dopamine (DA) from these novel hydrogels.

Main Methods:

• Modular chemoselective assembly of HA precursors with heterobifunctional linkers.
• Utilizing photo-labile ortho-nitrobenzyl groups for cross-linking and drug conjugation.
• Employing hydrazone cross-linking and orthogonal conjugation strategies.
• Characterization using rheology, spectrophotometry, chromatography, and mass spectrometry.

Main Results:

• Successfully prepared photo-degradable HA hydrogels via hydrazone cross-linking.
• Constructed a light-triggered hydrogel prodrug with dopamine (DA) conjugated via a photo-labile linker.
• Achieved on-demand DA release upon UV light exposure, with 11-fold less release in the dark.
• Demonstrated controlled release of model drugs from the HA hydrogels.

Conclusions:

• Integrated photolabile components into hyaluronan for the first time.
• Developed a novel system for light-controlled drug release from HA-based hydrogels.
• Showcased the potential of these photosensitive hydrogels for advanced drug delivery applications.