Bio-based chitosan–carrageenan–MgO–flaxseed oil nanocomposite attenuates cisplatin-induced nephrotoxicity via coordinated redox, inflammatory, and apoptotic modulation

Cisplatin is a potent concurrent chemotherapy, but its clinical efficacy is limited by nephrotoxicity due to systemic concentrations exceeding tolerable doses and/or absence of safe prophylactic strategies. Here, we developed a novel bio-based controlled-release nanobiocomposite (CCMgFO NBC) by integrating MgO nanoparticles coated with flaxseed oil (MgO-FO) into chitosan–κ-carrageenan polyelectrolyte nanocarriers to provide nephroprotection with synergism among antioxidant, anti-inflammatory and anti-apoptotic mechanisms. FO, a natural a natural crop-derived material, behaved as an eco-friendly reducing/capping agent and bioactive coating for MgO, contributing to improved surface modification stability, controlled release of active substances, and biological activity due to its rich omega-3 fatty acids and antioxidant phytoconstituents. The physicochemical characterization of FTIR, XRD, SEM/TEM, EDX and zeta potential revealed that the nanobiocomposite possessed desired characteristics such as high entrapment efficiency (71.6 ± 1.2%), drug loading (29.1 ± 0.8%), positive zeta potential (+43.29 mV) and sustained release of Mg²⁺ and flaxseed oil in physiological conditions. In a rat model of cisplatin-induced acute kidney injury, intraperitoneal CCMgFO NBC at 7.5 mg/kg improved renal function significantly more than treatment with cisplatin alone, reducing serum urea (48.14%), creatinine (9.8%), NGAL (47.35%) and KIM-1 levels (62.45%). The protective effects involved restoring GSH and CAT, reducing 8-OHdG, inhibiting IL-23 expression, and preserving p53 and Bax histoarchitecture. This work's novelty lies in combining a natural bioactive oil with MgO nanoparticles and encapsulating it into a biopolymer-based carrier, creating a stable multifunctional nanocomposite for enhanced nephroprotection. This platform offers controlled release and coordinated regulation of oxidative, inflammatory, and apoptotic pathways, improving upon single-component systems. These findings support CCMgFO NBC's potential as an innovative green nanoplatform to mitigate cisplatin-induced renal toxicity, with broader biomedical and nanotechnological implications.