Abstract
<title>Abstract</title> <p>Nephrotoxicity is a condition where the kidneys sustain damage from exposure to chemicals, toxins, or pharmaceuticals, which can lead to chronic kidney disease and decreased kidney function.The liposomal formulation of Ligustrazine was prepared by thin-film hydration using phospholipids, cholesterol, and surfactants. The optimized batches were characterized for particle size, polydispersity index, zeta potential, cumulative drug release, entrapment efficiency, and morphology using Scanning Electron Microscopy and Transmission Electron Microscopy. The optimized batch was then coated with an optimal concentration of polyethyleneimine and evaluated using the same parameters as the uncoated formulation. Molecular docking studies were performed to explore the interaction of Ligustrazine-loaded liposomes with soluble epoxide hydrolase and Nuclear Factor kappa-B. Molecular docking studies were conducted to elucidate the interactions of Ligustrazine with soluble epoxide hydrolase (sEH) and Nuclear Factor of kappa-light-chain-enhancer of activated B cells (NF-κB). A comprehensive comparison of the nephroprotective effects of Ligustrazine-loaded liposomes and polyethyleneimine-coated Ligustrazine-loaded liposomes was done by administering 1 g/kg of Acetaminophen orally to all groups of male Wistar rats weighing between 150-200 g for 7 days. A decrease in body weight, along with changes in blood urea nitrogen levels, serum creatinine, various biochemical markers, and histological damage, indicated nephrotoxicity and the effects of treatment. In vivo studies showed that polyethyleneimine-coated Ligustrazine-loaded liposomes were suitable for targeted drug delivery to the kidney and effectively delivered Ligustrazine, as further confirmed by docking analysis. The docking analysis revealed that Ligustrazine binds effectively to both sEH (3ANS) and NF-κB (1SVC), with docking scores of -5.184 kcal/mol and -1.744 kcal/mol, respectively. Overall, the findings suggest that the developed polyethyleneimine-coated Ligustrazine-loaded liposomes are promising candidates for treating nephrotoxicity.</p>