Rutin‐Loaded Dextran Selenium Nanoparticles as a Protective Strategy Against Paracetamol‐Induced Hepatotoxicity

Abstract Paracetamol (PCM) induced liver injury is a major clinical concern, primarily driven by oxidative stress and inflammation. This study aimed to develop and evaluate rutin‐loaded dextran selenium nanoparticles (Rutin‐Dex‐Se NPs) as a novel hepatoprotective formulation. The nanoparticles were synthesized via a green method using dextran as a stabilizer and characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X‐ray diffraction (XRD), scanning electron microscope (SEM), particle size, and zeta potential analyses. Rutin–Dex–Se NPs demonstrated a spherical morphology, an average particle size of 177.1 ± 1.01 nm, a zeta potential of +26.07 ± 0.87 mV, and high entrapment efficiency (92% ± 1.13%). The formulation showed sustained drug release (91.03% over 72 h) and enhanced antioxidant activity (IC 50 = 3.11 µg/mL) compared to free rutin. In vitro, the nanoparticles reduced H 2 O 2 ‐induced cytotoxicity and lactate dehydrogenase (LDH) release in WRL 68 liver cells. In vivo, pretreatment with Rutin–Dex–Se NPs in PCM‐induced hepatotoxic rats significantly restored serum biochemical markers, suppressed oxidative stress and pro‐inflammatory cytokines, and improved liver histopathology. These findings suggest that Rutin–Dex–Se NPs markedly enhance the therapeutic potential of rutin and represent a promising approach for managing PCM‐induced hepatotoxicity.