Peripheralization of centrally-acting cannabinoid-1 receptor antagonists by nanoparticles for the treatment metabolic related conditions

A nanocarrier comprising a cannabinoid 1 receptor (CB1R) antagonist, wherein said nanocarrier is configured for peripheralization of the CB1R antagonist contained therein, without inducing a CNS effect, and wherein the nanocarrier is an acid-terminated or an ester terminated PLGA having a molecular weight between 30 and 100 kDa.

A peripherally restricted nanocarrier comprising a central nervous system (CNS) acting CB1R antagonist, for selective modulation of a peripheral CB1R, wherein the nanocarrier is PLGA nanocarrier having a size between 100 and 300 nm and a zeta potential between zero and −10 (minus 10) mV, and wherein the PLGA is an acid-terminated or an ester terminated PLGA having a molecular weight between 30 and 100 kDa.

A method of peripheralization of a CNS-active CB1R antagonist without inducing CNS-derived side effects, the method comprising containment of said CNS-active CB1R antagonist in nanocarriers and administering said nanocarriers to the subject.

A method of treating or preventing a non-alcoholic fatty liver disease (NAFLD) or type 2 diabetes (T2D) or dylipidemia in a subject, the method comprising administering to said subject a composition comprising nanocarriers comprising a CB1R antagonist suitable for treatment or prevention of the NAFLD or T2D, wherein said nanocarrier is configured for peripheralization of the CNS acting CB1R antagonist, without inducing a CNS effect.

A pharmaceutical comprising a plurality of nanocarriers, each containing at least one CB1R antagonist and/or a CNS-active CB1R antagonist, wherein the pharmaceutical composition is an injectable composition suitable for administration to a subject, wherein the nanocarriers are of a size, surface charge and composition selected to prevent the nanocarriers from crossing the brain blood barrier of the subject.