# Part II: The Influence of Crosslinking Agents on the Properties and Colon-Targeted Drug Delivery Efficacy of Dextran-Based Hydrogels

## TL;DR

This study explores how different crosslinking agents affect dextran-based hydrogels for colon-targeted drug delivery, finding that DMAAazoB-based gels are effective for controlled release in the intestinal environment.

## Contribution

The study introduces azo-crosslinked dextran hydrogels as a novel platform for colon-targeted drug delivery with optimized swelling and release properties.

## Key findings

- DMAAazoB-crosslinked hydrogels showed the highest swelling at pH 3 and pH 6 with low mechanical strength.
- Uracil release was significant in the intestinal environment, especially in Dex-DMAAazoB hydrogels.
- Dex-DMAAazoB hydrogels exhibited antibacterial activity against E. coli and S. epidermidis.

## Abstract

In this study, dextran-based hydrogels were synthesized in dimethyl sulfoxide via free-radical polymerization with three structurally different crosslinking agents: divinyl benzene (DVB), diethylene glycol diacrylate (DEGDA), and 4,4′-di(methacryloylamino)azobenzene (DMAAazoB). Their morphology, swelling ability, mechanical properties, and potential for controlled release of the model substance (uracil) were examined, with the results showing that the chemical structure and chain length of the crosslinking agents significantly influence the structural and functional properties of hydrogels. Hydrogels crosslinked with DMAAazoB showed the highest swelling ability at pH 3 and pH 6 (2552 and 1696%, respectively), associated with protonation effects and sponge-like morphology, while simultaneously showing the lowest mechanical strength (20 and 47 MPa). In vitro simulations of gastrointestinal digestion showed that uracil was not released in the gastric phase, while in the intestinal environment, the release was significant, especially in Dex-DMAAzoB hydrogels (88.52%). The absence of azoreductases in the simulated system indicates that the release of the drug in real conditions would likely be even more pronounced. The Dex-DAAazoB hydrogel exhibited a slight antibacterial effect, producing inhibition zones of 8 and 7 mm against Escherichia coli ATCC 8739 and Staphylococcus epidermidis ATCC 12228, respectively. In contrast, the remaining hydrogel formulations showed no detectable antibacterial activity toward either bacterial strain, indicating their microbiological inertness and supporting their suitability as carrier matrices for antitumor drug delivery in colorectal cancer therapy. The obtained results confirm that azo-crosslinked dextran hydrogels, with an optimized amount of crosslinking agent, are promising carriers for the targeted and controlled delivery of antitumor drugs to the colorectal region.