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Acute kidney injury is characterised by abrupt failure of kidney function, sometimes leading to chronic kidney disease, and is associated with significant morbidity and mortality. However, there is no clear effective therapeutic solution and treatment is mainly based on either alleviation or removal of the possible cause and/or renal replacement therapy. Oxidative stress has been indicated as one of the main pathophysiological pathways in the development of acute kidney injury. Various treatments including antioxidants, inflammatory mediators and genetic modifiers have been proposed to for the treatment of this condition. Epidemiological studies show lower incidence of kidney failure with higher consumption of antioxidants. However, the data is inconclusive due to their physicochemical properties, bioavailability or toxicity. Novel drug delivery systems such as liposomes and nanoparticles have been proposed to overcome the pharmacodynamic and pharmacokinetic barriers. This review provides a brief introduction to acute kidney injury and the different factors involved in its pathology, focusing on oxidative stress. It also covers details of antioxidant use as preventive and/or treatment option. It will summarise their limitations as free drugs and the possible improvement in their bioavailability by two main novel drug delivery systems: liposomes and polymeric nanoparticles. Other therapies such as inflammatory mediators and genetic modifiers are also discussed briefly.