NANOTHERAPY TO DELAY COGNITIVE IMPAIRMENT: USING COLLOIDAL NANOCARRIERS TO BLOCK AMYLOID-β-INDUCED DAMAGE IN BRAIN CELL MEMBRANES

Abstract

Background: Numerous published studies indicate that microvascular endothelial dysfunction precedes cognitive decline in Alzheimer's disease, and that preservation of a healthy cerebrovascular endothelium can be an important therapeutic target. Methods: 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. Documented similarities in lipid composition between high-density lipoproteins (HDL) and the biomimetic (nanoemulsion) nanocarrier particles can partially simulate or mimic the known heterogeneity (i.e., subpopulations or subspecies) of HDL particles. Moreover, the above-described type BI scavenger receptor (i.e., either SR-BI (rodent) and/or CLA-1 (human) orthologs) has been shown to be a multifunctional receptor able to bind a broad variety of ligands, including HDL and chylomicron remnants. Results: Such colloidal-nanocarrier targeting allows for various Alzheimer's-related cell types to be simultaneously searched out, in vivo, for localized drug treatment. Using various lipids and their mixtures to form self-assembled non-lamellar nanostructures, it has continually been reported possible to successfully obtain stable colloidal dispersions of (liquid-crystalline) lipid cubic phases with well-defined particle size and morphology. In particular, within the range of self-assembled phases in model surfactant-like lipid systems, various investigators further emphasize that monglyceride-based lyotropic liquid-crystalline phases are relatively unique owing to their rich polymorphism in water and potential application as drug nanocarriers. Conclusion: This (colloidal-nanocarrier) in vivo targeting advantage may be particularly important for repurposing an FDA-approved drug, especially one which has shown the added ability to restore some cognitive functions in certain animals models of Alzheimer's disease (e.g., the anticancer drug bexarotene). Bexarotene (and several analogs or other candidate-repurposing drugs) up to now, by itself (i.e., without nanocarrier), displayed poor CNS penetration in human subjects.

Biomaterial to Improve Drug Delivery in Alzheimer's Disease: Linking Major Pathogenic Pathways

“…By incorporating appropriate drug(s) into biomimetic (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cellsurface scavenger receptors, and crosses the blood-brain barrier (BBB). Such targeting allows for various Alzheimer's-related cell types to be simultaneously searched out, in vivo, for localized drug treatment [3][4][5][6]. This (colloidal-nanocarrier) in vivo targeting advantage may be particularly important when delivering pleiotropic natural substances (e.g., an isoflavone) or for repurposing FDA-approved food additive(s) and/or drug(s), especially one which has shown the added ability to restore some cognitive functions in certain animal models of Alzheimer's disease [4].…”