Oxidative-stress-responsive polymeric nanocarriers for Alzheimer’s disease: emerging antioxidant strategies using NAC and curcumin

Abstract

A complex combination of oxidative stress, mitochondrial dysfunction, neuroinflammation, and protein aggregation initiates Alzheimer disease (AD), and redox imbalance becomes an initial and lead pathological process. Traditional antioxidants like N-acetylcysteine (NAC) and curcumin demonstrate high mechanistic capacity but have poor stability, are rapidly metabolicized and have low blood-brain barrier (BBB) penetration. Polymeric nanocarriers can be a solution to these drawbacks, as they offer controlled delivery, better targeting to the brain, and dynamic delivery in response to microenvironmental changes. This review is a synthesis of recent developments in oxidative-stress-responsive polymeric systems (PLGA-, chitosan-, and hybrid polymer-based nanoparticles) designed to be used in precise redox modulation. We emphasize the therapeutic synergies of co-delivery of dual NAC-curcumin that is backed with in-vitro and in-vivo results of enhanced antioxidant activity, mitochondrial integrity, and cognitive improvements in AD models. The most important translational obstacles such as nanoparticle scalability, regulatory obstacles, and interpatient heterogeneity are acutely addressed, as well as new developments such as AI-driven formulation design and personalized oxidative biomarker profiling. All these innovations put redox-targeted nanomedicine as a prospective next-generation therapy of AD.