A nanoparticle drug delivery vehicle and formulation containing HPßCD and optimized for delivery to endo/lysosomes for treatment of NPC. Lipid nanoparticle vehicles loaded with HPßCD have been characterized and cholesterol reduction demonstrated in MEF NPC KO cells. Because NPC1 affected cells have high aggregation of cholesterol in the endo/ lysosomal system, it is advantageous to deliver HPßCD to the endo/lysosomes. The lipid nanoparticles vehicles may exploit endo/lysosomal pathways to get inside of cells. Once inside, the vehicles release a therapeutic amount of the therapeutic agent into the endo/lysosome vesicles, which due to proximity to cholesterol aggregated in the endo/lysosomal system and due to high concentration of lipid nanoparticles drug delivery vehicles in the endosome, triggers improved clearance of cholesterol.
Features & Benefits
Background of Invention
Niemann-pick type C (NPC) is a lipid storage disorder characterized by buildup of cholesterol in late endosomes/lysosomes. The inability to clear cholesterol leads to hepatic and pulmonary dysfunction and neurodegeneration. This devastating disorder is always fatal, often before age ten. Clearance of cholesterol using 2-hyrdoxypropyl-ß-cyclodextrin (HPßCD) has been shown to be an effective strategy for treatment of pre-clinical animal models of NPC1 disorder; however, extremely high concentrations of HPßCD are necessary to achieve therapeutic effects. Because the drug fails to cross the blood brain barrier (BBB), alleviating neurodegeneration requires direct brain injections that increase the toxicity profile of HPßCD.
Patent pending; available for exclusive licensing