Carotenoid containing cationic nanoparticles for effective therapy for suppressing oxidative stress: An intranasal approach

Abstract

Alzheimer's disease is the most common type of dementia. Oxidative stress is involved in the progression of aging and Alzheimer's disease. It is known that lutein is a carotenoid having antioxidant properties. The present research explores Lutein loaded chitosan nanoparticles for Suppressing Oxidative Stress in the treatment of Alzheimer's. The developed nanoparticles are administered through the nose to target brain via nose-to-brain pathway. For optimization of formulation a systematic QbD approach was used. The developed nanoparticles further characterized for Physicochemical parameters, Morphology, In-vitro drug releases, Ex-vivo diffusion, In-vitro Cell viability, cellular uptake, In-vitro BBB Permeation, antioxidant properties, In-vivo biodistribution, and stability study. The developed nanoparticles' surface morphology suggested homogeneously dispersed spherical nanoparticles having < 200 nm size. The drug release study demonstrate the controlled release of lutein for more than 96 h while less than 50% lutein was released after 24 h in an ex-vivo diffusion study. The cell cytotoxicity assay confirms the nontoxicity of l-CNPs. The cellular uptake study shows enhanced internalization of l-CNPs through the caveolae-mediated endocytosis pathway. The ROS generation confirmed the absence of any significant ROS generation nanoparticles. The antioxidant assay shows significant ROS scavenging activity of l-CNPs. In-vitro BBB permeation demonstrates the efficient passage of l-CNPs through BBB compared to pure lutein. This was further supported by bio-distribution demonstrating the deposition of nanoparticles in the brain through nasal administration. The acquired outcomes prove the possible activities of lutein-loaded l-CNPs for reducing oxidative stress in the brain for Alzheimer's treatment.