Therapeutic potential of alginate-stabilized silver nanoparticles encapsulating nitrogen-containing heterocyclic derivative mitigates inflammation and fibrosis in L-arginine induced in vivo zebrafish model of chronic pancreatitis.

Pancreatic fibrosis results from chronic pancreatitis, a critical pathological hallmark of pancreatitis and pancreatic insufficiency. This research explore the potential of synthesised nitrogen-containing heterocyclic indoline derivative (IB) encapsulated in alginate-capped silver nanoparticle (AG + IB) therapeutic against L-arginine (LAG) induced pancreatic fibrosis in adult zebrafish. AG + IB nanoconjugate were synthesised and characterized by UV-Vis spectrophotometer, FTIR, XRD, zeta potential, Tyndall effect and SEM/TEM analyses, confirming successful drug loading, a uniform morphological structure, stable dispersion, and pH-responsive release. In-vitro analysis demonstrated enhanced nitric oxide scavenging and protease inhibition by AG + IB compared to IB alone. Developmental toxicity assays confirmed 20 μM as safe and effective dose for in-vivo studies. LAG exposure significantly increases inflammatory stress in zebrafish pancreatic tissue leading to severe damage and reduced pancreatic function. However, AG + IB treatment markedly restored pancreatic architecture by decreased collagen deposition, normalized blood glucose level, and reversed oxidative stress. Additionally, restoring pancreatic architecture and alleviating oxidative stress normalized exocrine enzyme levels. Molecular analyse showed AG + IB downregulated key inflammatory markers, fibrogenic and remodelling genes. Histopathological examination further confirmed substantial protection against acinar cell atrophy, insulitis and fibrosis. These results indicate AG + IB holds great promise as a biocompatible nanotherapeutic for targeting chronic pancreatitis by modulating inflammation and oxidative stress.