Silver nanoparticle-conjugated pyrimidine-based BN6 methanimine derivative improves DSS-induced inflammatory bowel disease in zebrafish.

BACKGROUND

Treatment for inflammatory bowel diseases (IBD) include immunosuppressant and steroids for managing the inflammation. Also, these treatments have many negative complications, limited efficacy, and development of drug resistance.

OBJECTIVE

To synthesize the (Z)-N-(4-(2-chlorophenyl)-6-(4-nitrophenyl)pyrimidin-2-yl)-1-(furan-2-yl)methanimine (named BN6) derivative and examines its anti-inflammatory, antioxidant, and drug-delivery effectiveness of silver nanoparticle (AgNPs) nanoconjugates against dextran sulfate sodium (DSS) induced IBD in an in-vivo zebrafish model.

METHODS

The synthesis and evaluation of AgNPs-BN6 derivatives conducted through in vitro studies. The drug release profile was studied at pH 7.0, simulating intestinal conditions, and the entrapment efficiency was evaluated across a range of concentrations, from 10 to 160 μM. Inflammatory marker levels (tnf-α, il-1β, cox-2, and il-10), biochemical changes (SOD, CAT, GSH, and LDH), macrophage localization, oxidative stress and cellular damages were measured in a following AgNPs-BN6 treatment at concentrations of 40 μM, 80 μM, and BN6 (100 μM).

RESULTS

AgNPs-BN6 conjugate drug release at 80 μM peaked at over 80% within 5 h under intestinal pH, with a slight decrease noted at 10 h. The highest entrapment efficiency, 82.30 ± 0.25, was observed at 80 μM, showcasing a dose-dependent increase until that concentration. In the model group, inflammatory markers tnf-α, il-1β, and cox-2 were particularly elevated, signaling inflammation, whereas AgNPs-BN6 treatment at 80 μM effectively lowered these markers, reinstating balance with inflammatory genes. Additionally, AgNPs-BN6 treatment reduces oxidative stress markers, demonstrating its antioxidant properties.

CONCLUSION

AgNPs-BN6 derivatives, especially at 80 μM, possess substantial anti-inflammatory and antioxidant properties, emphasizing their potential as effective therapeutic agents for inflammatory disease.

CLINICAL TRAIL: Not Applicable.