Articles - Nano Progress

Abstract

Much evidence has been published which indicates that microvascular endothelial dysfunction, due to cerebrovascular risk factors (e.g., atherosclerosis, hypertension, obesity, diabetes, smoking, aging), precedes cognitive decline in Alzheimer's disease and contributes to its pathogenesis. By incorporating appropriate drug(s) into biomimetic (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the blood-brain barrier (BBB). Documented similarities in lipid composition, between naturally occurring high-density lipoproteins (HDL) and the artificial biomimetic (nanoemulsion) nanocarrier particles, can partially simulate or mimic the known heterogeneity (i.e., subpopulations or subspecies) of HDL particles. Such biomedical application of colloidal drug-nanocarriers can potentially be extended to the treatment of complex medical disorders like dementia. The cardiovascular risk factors for dementia trigger widespread inflammation and oxidative stress; these two interacting processes involve pathophysiological cascades which lead to neuronal Ca²⁺ increase, neurodegeneration, gradual cognitive/memory decline, and eventually (late-onset) dementia. In particular, recent research indicates that chronic inflammatory stimulus in the gut may induce (e.g., via serum amyloid A (SAA)) the release of proinflammatory cytokines. At the same time, increased BBB permeability due to aging (or dysfunction), in turn, allows these proinflammatory cytokines to enter the brain, inducing glia reactivity. These recent findings, and various past studies, indicate that inflammation plays an important role in the process of Aβ deposition and, therefore, the inhibition of inflammatory cascades may attenuate amyloidogenic processes—such as Alzheimer's disease. Hence, an effective preventive and therapeutic strategy could be based upon nanotargeting drug(s), using lipid nanocarriers, toward a major SAA receptor responsible for numerous SAA-mediated cell signaling events leading to cognitive decline and eventually Alzheimer's disease or (late-onset) dementia.