Work

Dynamic Hydrazone-Crosslinked Hyaluronic Acid Hydrogels with Dual-Responsive Nanoparticles for Controlled Hydrophobic Drug Release

Year: 2026

Type: article

Abstract: Many hydrogel-based drug delivery systems suffer from poor release control, particularly undesirable initial burst release, limiting sustained delivery. Here, we developed a dual stimuli-responsive hyaluronic acid (HA) hydrogel-nanoparticle system to regulate release through coordinated matrix- and carrier-level responsiveness. Aldehyde-functionalized HA (HA-Ald) was crosslinked with a disulfide-containing hydrazide linker, forming dynamic hydrogels with reversible hydrazone bonds and redox-cleavable disulfide linkages. Nile Red-loaded nanoparticles (NR-NPs), composed of a light- and redox-responsive triblock copolymer containing disulfide linkages and terminal coumarin groups, were incorporated as model drug carriers. Reductive conditions simultaneously triggered hydrogel degradation and nanoparticle destabilization through shared disulfide chemistry, while UV light (365 nm) provided an orthogonal trigger for nanoparticle-mediated release. Fluorescence studies revealed an initial increase in NR intensity due to migration into hydrophobic domains, followed by gradual decline from network degradation and dye diffusion. These results indicate that the coordinated self-healing hydrogel-nanoparticle system improves release control while reducing burst release.

Source: Biomacromolecules

DOI: 10.1021/acs.biomac.6c01618

Authors: Shibam Pal, Taha Behroozi Kohlan, Nancy Ferrentino, Daniela Pappalardo, Anna Finne-Wistrand

Institutions: KTH Royal Institute of Technology, University of Sannio

Language: English

Topic: Hydrogels: synthesis, properties, applications

Subfield: Molecular Medicine

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500