Curcumin-er, a liposomal-plga sustained release nanocurcumin for minimizing qt prolongation for cancer therapy

Abstract

The present invention includes compositions and methods of making a nanoparticle composition comprising a polymeric core comprising one or more polymers and one or more active agents, and at least one layer of one or more lipids on the surface of the polymeric core; more specifically, the invention relates to the use of curcumin within such a lipid-polymer nanoparticle formulation for minimizing QT prolongation associated with curcumin in treatment of cancer.

What is claimed is: 
     
         1 . A composition for treating cancer comprising:
 a polymeric nanoparticle core comprising one or more polymers and at least one of curcumin or curcuminoids; and   at least one layer of one or more lipids on the surface of the polymeric core, wherein the at least one of the curcumin or curcuminoids nanoparticles, wherein the composition does not cause QT prolongation when provided to a subject.   
     
     
         2 . The nanoparticle composition of  claim 1 , wherein the one or more polymers comprise at least one of poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid), polylactide (PLA), or poly-L-lactide-co-ε-caprolactone (PLCL). 
     
     
         3 . The nanoparticle composition of  claim 1 , wherein the composition further comprises an active agent selected from at least one of an anti-cancer drug, an antibiotic, an antiviral, an antifungal, an antihelminthic, a nutrient, a small molecule, a siRNA, an antioxidant, and an antibody, or a conventional radioisotope. 
     
     
         4 . The nanoparticle composition of  claim 1 , wherein the one or more lipids comprise at least one of dimyristoyl phosphatidylcholine (DMPC), dimyristoyl phosphatidylglycerol (DMPG), 1,2-dioctadecanoyl-sn-glycero-3-phosphoethanolamine (DSPE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol) (DSPE-PEG), DMPE PEG, maleimide, lecithin, cholesterol, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (ammonium salt), and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) (ammonium salt). 
     
     
         5 . The nanoparticle composition of  claim 1 , wherein the one or more lipids comprise dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylglycerol (DMPG) in a molar ratio of 9:1, 7:3, 8:2, or 7.5:2.5. 
     
     
         6 . The nanoparticle composition of  claim 1 , further comprising at least one targeting agent, wherein the targeting agent selectively targets the nanoparticle to diseased tissue/cells, thereby minimizing whole body dose. 
     
     
         7 . The nanoparticle composition of  claim 1 , further comprising at least one targeting agent, wherein the targeting agent comprises an antibody or functional fragment thereof, a small molecule, a peptide, a carbohydrate, an siRNA, a protein, a nucleic acid, an aptamer, a second nanoparticle, a cytokine, a chemokine, a lymphokine, a receptor, a lipid, a lectin, a ferrous metal, a magnetic particle, a linker, an isotope and combinations thereof. 
     
     
         8 . The nanoparticle composition of  claim 1 , wherein the nanoparticles have a size of 90 to 150 nm. 
     
     
         9 . The nanoparticle composition of  claim 1 , wherein a bioavailability of the active agent is increased, a QT prolongation is reduced, and the active agent is released in a sustained manner. 
     
     
         10 . The nanoparticle composition of  claim 1 , wherein the nanoparticles are adapted for intramuscular, subcutaneous, intravascular, or intravenous administration. 
     
     
         11 . A method of forming a nanoparticle composition comprising:
 forming an organic phase by combining one or more polymers, one or more solvents and at least one of curcumin or curcuminoids;   forming a lipid aqueous phase by mixing one or more lipids with water;   mixing the organic phase with the lipid aqueous phase, whereby an emulsion is formed; and   incubating the emulsion, whereby self-assembly of nanoparticles occurs and wherein the curcumin or curcuminoids nanoparticles does not cause QT prolongation when provided to a subject.   
     
     
         12 . A method for treating a patient suspected of being afflicted with a disease comprising administering nanoparticles, wherein the nanoparticles comprise a polymeric core comprising one or more polymers and one or more active agents and at least one layer of one or more lipids on the surface of the polymeric core, wherein the active agent is suspected of causing QT prolongation when provided to a subject. 
     
     
         13 . The method of  claim 12 , wherein administering nanoparticles comprises administering the nanoparticle by intramuscular, subcutaneous, intravascular, or intravenous administration. 
     
     
         14 . The method of  claim 12 , wherein the disease is selected from the group consisting of neurologic, oncologic, and metabolic diseases. 
     
     
         15 . The method of  claim 12 , wherein the disease is selected from the group consisting of Parkinson's disease, Alzheimer's disease, multiple sclerosis, ALS, sequel, behavioral and cognitive disorders, autism spectrum, depression, and neoplastic disease. 
     
     
         16 . The method of  claim 12 , wherein the active agent is released in a sustained manner. 
     
     
         17 . A pharmaceutical agent comprising:
 a nanoparticle for drug delivery comprising a polymer, an active agent that causes QT prolongation, and at least one layer of one or more lipids encapsulating the polymer and the active agent and the agent does not cause QT prolongation.   
     
     
         18 . A method for treating a patient suspected of being afflicted with a disease, the method comprising administering nanoparticles, wherein the nanoparticles comprise a polymeric core comprising one or more polymers, curcumin, and at least one layer of one or more lipids on the surface of the polymeric core, wherein treating the patient does not cause QT prolongation. 
     
     
         19 . A method of treating a subject suspected of having cancer comprising:
 identifying that a patient suspected of having a cancer; and   Providing the subject with an amount of at least one or curcumin or curcuminoids in an amount sufficient to reduce the cancer in the subject, wherein the at least one or curcumin or curcuminoids are in a polymeric nanoparticle core comprising one or more polymers and at least one of curcumin or curcuminoids; and   at least one layer of one or more lipids on the surface of the polymeric core, wherein the at least one of the curcumin or curcuminoids nanoparticles does not cause QT prolongation when provided to a subject.   
     
     
         20 . The method of  claim 19 , wherein the cancer is a pancreatic, a prostate, or a breast cancer.