Delaying Dementia: Targeted Brain Delivery Using Lipid Cubic Phases

Microvascular endothelial dysfunction precedes, often by decades, the cognitive decline associated with Alzheimer's disease. Hence, preservation of a healthy cerebrovascular endothelium can be an important therapeutic target. 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 – among 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. Such colloidal-nanocarrier targeting allows for various Alzheimer's-related cell types to be simultaneously searched in a holistic integrative approach, in vivo, for localized drug treatment. Using various biobased 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, monoglyceride-based lyotropic liquid-crystalline phases are relatively unique owing to their rich polymorphism in water and potential application as drug nanocarriers. This (colloidal-nanocarrier) in vivo targeting advantage may be particularly important when delivering pleiotropic natural substances (e.g., an isoflavone) or for repurposing an FDA-approved drug.