Chitosan nanoparticle encapsulated pentoxifylline improves renal protection and reduces oxidative stress in amikacin induced nephrotoxicity

Abstract Amikacin (AMK)-induced nephrotoxicity remains a clinical challenge, necessitating innovative therapeutic strategies. This study developed pentoxifylline-loaded chitosan nanoparticles (PTX-CSNPs) to enhance PTX’s renoprotective effects while minimizing its side effects. PTX-CSNPs were synthesized via ionic gelation, exhibiting high entrapment efficiency (89.53%) and sustained release (87% at 48 h). Characterization revealed spherical nanoparticles (30-50 nm by TEM and 79.05 nm by DLS) with positive zeta potential (+ 32.77 mV), confirmed by FTIR and XRD analyses. In vitro, PTX-CSNPs demonstrated superior antioxidant (98.73% DPPH scavenging), anti-inflammatory (76.46% RBCs membrane stabilization), and anticoagulant activity compared to free PTX. In vivo, AMK-induced nephrotoxic rats treated with PTX-CSNPs showed normalization of renal function biomarkers (BUN, creatinine, uric acid) and oxidative stress markers (MDA, SOD, GSH), alongside reduced inflammatory markers levels outperforming free PTX or CSNPs alone. Histopathology revealed preserved glomerular and tubular architecture. The nanoformulation’s efficacy was attributed to chitosan-mediated targeted delivery and PTX’s anti-inflammatory/antioxidant synergy. These findings highlighted PTX-CSNPs as a promising nanotherapeutic for drug-induced kidney injury, offering enhanced bioavailability and reduced systemic toxicity. Graphical abstract