Drug nanotargeting for treatment of neurodegeneration and aging
Microvascular endothelial dysfunction precedes, often by decades, the cognitive decline associated with Alzheimer’s disease. Accordingly, cerebrovascular risk factors (e.g., atherosclerosis, diabetes, aging) contribute to the pathogenesis of this common neurodegenerative disease. By incorporating appropriate drug(s) into biobased (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. This (intravenous) combination therapeutic, known to be a successful drug carrier, would make it possible for various cell types within the brain (all potentially implicated [see below] in Alzheimer’s disease) to be simultaneously nanotargeted for localized drug delivery via cell-surface SR-BI. Hence, such colloidal-nanocarrier targeting allows for various Alzheimer’s-related cell types to be simultaneously searched in a holistic integrative approach. This (colloidal-nanocarrier) targeting advantage, in vivo, may be particularly important when delivering pleiotropic natural substances (e.g., a flavonoid) or for repurposing an FDA-approved drug. For example, the described/proposed colloidal (nanoemulsion) nanocarrier is especially useful for the delivery of low-molecular-weight compounds having a significant degree of lipophilicity (i.e., low water solubility), such as various pleiotropic natural substances (e.g., the plant polyphenol known as “resveratrol”, commonly used as a dietary supplement).
Keywords: Alzheimer’s disease, cognitive impairment, nanoemulsion, SR-BI, vascular dementia