Stimuli-Sensitive Dextran Hydrogel Composited with Clickable Reaction-Based Aggregation-Induced Emission Micelles: A Carrier of Hydrophobic Drugs

Introducing hydrophobic microstructures into polymer hydrogels has been considered recently as an effective strategy to design multifunctional hydrogel-based carriers for hydrophobic drug delivery. Herein, fluorescent micelle-hydrogel composites by combining aggregation-induced emission (AIE)-active polyethylenimine (PEI) micelles into a dextran hydrogel matrix for improving the delivery of doxorubicin (DOX) are presented. A synthetic protocol based on the mercaptoacetic acid locking imine (MALI) reaction was explored to effectively modify the side-chains of alkylated polyethylenimine (PEI-C-12) with AIEgens (aldehyde-functionalized tetraphenylethene, TPE-CHO). DOX-loaded micelle nanoparticles with AIE fluorescent properties and fluorescence resonance energy transfer (FRET) phenomenon were obtained via the self-assembly of the resulting amphiphilic TPE-PEI-C-12 and then encapsulated into dextran hydrogels formed by the disulfide-containing Schiff base reaction. The stimuli-sensitive release of the DOX-loaded AEI micelles from the hydrogel matrix and the following DOX release via demicellization was finally investigated by in vitro release and cell-labeling studies. The above results suggest that the AIE micelle-hydrogel system can be considered as a valuable carrier of hydrophobic drugs with potential in intracellular imaging and drug release tracing, especially for local drug delivery.

Automated summary

Introducing hydrophobic microstructures into polymer hydrogels has been considered as an effective strategy for hydrophobic drug delivery. In this study, fluorescent micelle-hydrogel composites were formed by combining AIE-active polyethylenimine (PEI) micelles into a dextran hydrogel matrix. The release of doxorubicin (DOX) loaded in the micelles and the following drug release from the hydrogel matrix were investigated. The results suggest that this AIE micelle-hydrogel system could be a valuable carrier for hydrophobic drugs with potential applications in intracellular imaging and drug release tracing.