Methods for Improving Drug Delivery to the Central Nervous System

The invention relates to the uses of the tricyclic antidepressant amitriptyline, its bioactive metabolites, and other LPA1R activators to improve the bioavailability and delivery of therapeutics to the central nervous system. This invention demonstrates that amitriptyline and other agents selectively decreaseP-glycoprotein (P-gp) transport activity by ligand activation of lysophosphatidic acid 1 receptor (LPA1R) at the blood-brain barrier.P-gp is an effective target for increasing drug delivery to the brain (CNS) for two major reasons: (1) its substrates include a large portion of on-the-market drugs, including chemotherapeutics, and (2) its directionality results in a net efflux of drugs from the brain. Additionally, specifically targetingP-gp through LPA1R activation bypasses the clinical challenges resulting from the toxicity of substrate inhibitors ofP-gp. This invention describes the inhibition of drug efflux byP-gp transport; thus, co-administration of therapeutics with amitriptyline and other LPA1R activators provides a method for increasing drug delivery to the CNS, and improving overall drug efficacy. Moreover, drug delivery to other barrier tissues will also be enhanced where a similar LPA1R-P-gp activity relationship exists.IC: NIEHSNIH Ref. No.: E-179-2016-0Applications: Drug delivery to the CNSCo-administration of therapeuticsBlood-brain-barrier permeabilityProvider Technology ID: 3093Updated On: Apr 18, 2018Provider Classifications: ...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research