Methods of permeabilizing the blood brain barrier

Abstract

The present invention relates to using monoterpene or sesquiterpene to permeabilize the blood brain barrier.

What is claimed is: 
     
         1 . A method of administering a therapeutic agent to a central nervous system of a mammal, the method comprising administering a monoterpene before or concurrently with the therapeutic agent. 
     
     
         2 . The method of  claim 1 , wherein the central nervous system is the brain. 
     
     
         3 . The method of  claim 1 , wherein the monoterpene is perillyl alcohol. 
     
     
         4 . The method of  claim 3 , wherein perillyl alcohol is administered intraarterially. 
     
     
         5 . The method of  claim 3 , wherein perillyl alcohol is administered at a dose ranging from about 0.050 mg/kg to about 500 mg/kg of body weight. 
     
     
         6 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         7 . The method of  claim 1 , wherein the monoterpene is administered from about 0.2 minutes to about 60 minutes before the therapeutic agent is administered. 
     
     
         8 . The method of  claim 7 , wherein the monoterpene is administered from about 1 minute to about 15 minutes before the therapeutic agent is administered. 
     
     
         9 . The method of  claim 1 , wherein the monoterpene and the therapeutic agent are administered separately. 
     
     
         10 . The method of  claim 1 , wherein the monoterpene and the therapeutic agent are administered concurrently. 
     
     
         11 . The method of  claim 10 , wherein the monoterpene and the therapeutic agent are administered together in a pharmaceutical composition. 
     
     
         12 . The method of  claim 1 , wherein the therapeutic agent is a chemotherapeutic agent. 
     
     
         13 . The method of  claim 12 , wherein the chemotherapeutic agent is selected from the group consisting of a DNA alkylating agent, a topoisomerase inhibitor, an endoplasmic reticulum stress inducing agent, a platinum compound, an antimetabolite, an enzyme inhibitor, a receptor antagonist, a therapeutic antibody, and combinations thereof. 
     
     
         14 . The method of  claim 12 , wherein the chemotherapeutic agent is dimethyl-celecoxib (DMC), irinotecan (CPT-11), temozolomide or rolipram. 
     
     
         15 . The method of  claim 1 , wherein the therapeutic agent is an antibody or antibody fragment. 
     
     
         16 . The method of  claim 1 , wherein the therapeutic agent is an immune cell expressing a chimeric antigen receptor. 
     
     
         17 . The method of  claim 16 , wherein the immune cell is a T cell. 
     
     
         18 . The method of  claim 16 , wherein the therapeutic agent is a CAR-T cell. 
     
     
         19 . The method of  claim 1 , wherein the monoterpene is administered by inhalation, intranasally, orally, intravenously, subcutaneously or intramuscularly. 
     
     
         20 . The method of  claim 1 , wherein the mammal has cancer. 
     
     
         21 . The method of  claim 20 , wherein the cancer is a tumor of the nervous system. 
     
     
         22 . The method of  claim 21 , wherein the tumor is a glioblastoma. 
     
     
         23 . The method of  claim 1 , further comprising treating the mammal with radiation.