Nanoparticles for drug delivery targeting neurodegeneration in brain and eye

Abstract

Abstract The treatment of certain neurodegenerative diseases is limited by inadequate delivery efficiency and nonspecific tissue distribution of the therapeutics. For therapeutics targeting the brain, they need to first cross the biological barriers separating the blood and the brain parenchyma, in particular the blood–brain barrier, to enter the targeted brain regions; for therapeutics targeting the eye, different layers of cornea, sclera, and retina including the blood–retinal barrier act as obstacles for delivery. The dynamic barriers (blood flow, lymphatic clearance, etc.) also hinder the effective delivery and accumulation of the therapeutics. One of the approaches is to use nanoparticles as delivery vehicles to transport therapeutics across these barriers to the targeted regions, especially to specific brain regions and retina. Subsequently, nanoparticles need to accumulate in certain brain or retinal regions, so that cargoes inside or attached to the nanoparticles can be released and more easily reach the effective concentration. This article aims to highlight the importance of drug distribution at specific brain and retinal regions for the treatment of different neurodegenerative diseases. To achieve this purpose, the criteria for choosing appropriate routes of administration, the challenges associated with respective biological barriers, the physiochemical properties as well as the stability and toxicity of nanoparticles, and also some specific properties required for delivering different cargoes are detailed. Commonly used therapeutics and gene therapy for treating neurodegeneration, along with opportunities and challenges will also be discussed.