ASCORBATE-LINKED NANOSYSTEMS FOR BRAIN DELIVERY

The invention is based, at least in part, on the discovery of a method for targeting liposomes and micelles to brain cells. This discovery was exploited to develop the invention, which, in one aspect, features a method of delivering a lipid formulation to brain cell, comprising contacting the brain cell with lipid formulation, the lipid formulation comprising ascorbate or an ascorbate derivative on an outer surface of the lipid formulation, the ascorbate or the ascorbate derivative contacting a sodium-dependent vitamin C transporter (SVCT) on the brain cell to thereby deliver the lipid formulation to the brain cell. In certain embodiments, the lipid formulation is a liposome or micelle. In particular embodiments, the ascorbate linked to the liposome or micelle is not bound by a glucose transporter (GLUT), or has reduced binding capacity to GLUT relative to free ascorbate. In some embodiments, the liposome or micelle comprises a phospholipid conjugated to the ascorbate or the ascorbate derivative at the C6 position of the ascorbate or the ascorbate derivative. In some embodiments the phospholipid comprises derivatized phospholipids. In particular embodiments the derivatized phospholipid comprises polyethylenglycol (PEG). In certain embodiments the ascrobate or ascorbate derivative is conjugated to the derivatized phospholipid via PEG. In some embodiments, the brain cell is an epithelial cell of the choroid plexus or an ependymal cell of the blood brain barrier. In some embodiments the brain cell trasports the liposome or micelle into the cerebrospinal fluid (CSF) of the brain. In other embodiments, after entering the CSF, the liposome or micelle contacts a second brain cell. In particular embodiments the second brain cell is a neuron, a glial cell, or an astrocyte or a brain turmor cell. In some embodiments the liposome or the micelle further comprises a therapeutic agent or a detection agent. In other aspect the invention features a method of delivering a therapeutic agent or a detection agent to a brain cell, comprising contacting the brain cell with a lipid formulation loaded with a therapeutic agent or detection agent, and ascorbate or an ascorbate derivative on the outer surface of the lipid formulation, the ascorbate or the ascorbate derivative contacting a sodium-dependent vitamin C transporter (SVCT) on the brain cell to thereby deliver the therapeutic agent or the detection agent to the brain cell.