Prophylactic administration of silica nanoparticles loaded with amifostine prevents cisplatin-induced nephrotoxicity...

Drug-induced nephrotoxicity is a major limitation in chemotherapy, particularly with cisplatin, necessitating effective renal-protective strategies. Amifostine, a thiol-based prophylactic agent, has potential to mitigate such toxicity. This study demonstrates a prophylactic nephroprotective strategy where SiNPs@AMF was administered prior to and during cisplatin treatment and development of novel nano-emulsified formulation to potentially overcome the limitations of free amifostine, such as its short half-life and systemic side effects. Hollow silica nanoparticles loaded with amifostine were prepared via ultrasonication and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. Fifty male Wistar rats were randomly assigned to five groups: normal control, nano-emulsion control (SiNPs), nephrotoxic (cisplatin), amifostine nano-emulsion (SiNPs@AMF), and combined treatment (SiNPs@AMF + cisplatin). Cisplatin-induced nephrotoxicity was established by intraperitoneal injections (20 mg/kg, twice day after day). Serum inflammatory and extracellular matrix biomarkers (HA, MMP-9, NF-κB, MCP-1) were quantified by ELISA.urea, creatinine by spectrophotometer. Renal microRNA (miR-29a, miR-193a) and podocyte markers (podocin, nephrin) were evaluated using quantitative real-time PCR. P53 expression was assessed via immunohistochemistry. Cisplatin markedly increased serum urea, creatinine, HA, MMP-9, NF-κB, and MCP-1, downregulated miR-29a, podocin, and nephrin, and upregulated miR-193a, accompanied by elevated P53 immunoreactivity. Treatment with SiNPs@AMF significantly attenuated inflammatory and extracellular matrix disruptions, restored miR-29a, podocin, and nephrin expression, reduced miR-193a overexpression, and decreased P53 staining. Silica nano-emulsified amifostine effectively mitigates cisplatin-induced nephrotoxicity by suppressing inflammation, preserving extracellular matrix integrity, and restoring renal microRNA balance. These findings support the therapeutic potential of nano-formulated thiol compounds as a targeted strategy to prevent chemotherapy-associated renal injury.