Custom-formulated phospholipid microbubbles and methods and uses thereof

Abstract

A phospholipid microbubble comprising a shell which comprises a plurality of polyunsaturated fatty acid (“PUFA”)-containing phospholipids, and a core of paramagnetic gas surrounded by the shell comprising the plurality of PUFA-containing phospholipids. The present invention also provides methods of delivering a prophylactically or therapeutically effective amount of PUFA to an area of disease or injury in a subject. The present invention also provides methods of preventing or treating a disease in a subject using a prophylactically or therapeutically effective amount of the aforementioned phospholipid microbubbles.

What is claimed is: 
     
         1 . A phospholipid microbubble comprising a shell which comprises a plurality of polyunsaturated fatty acid (“PUFA”)-containing phospholipids, and a core of paramagnetic gas surrounded by said shell comprising said plurality of PUFA-containing phospholipids. 
     
     
         2 . The phospholipid microbubble of  claim 1 , wherein said plurality of PUFA-containing phospholipids comprising a plurality of polar head groups, said plurality of polar head groups comprising phosphatidylserine (“PS”), phosphadtidylcholine (“PC”), phosphatidyl-ethanolamine (“PE”), phosphatidylinositol (“PI”), or a combination thereof. 
     
     
         3 . The phospholipid microbubble of  claim 1 , wherein said plurality of PUFA-containing phospholipids comprising a plurality of non-polar fatty acid tails, said plurality of non-polar fatty acid tails comprising an omega-3 PUFA, an omega-3 PUFA precursor, an omega-3 PUFA-derived metabolite, an omega-6 PUFA, an omega-9 PUFA, a conjugated linoleic acid, a conjugated linoleic acid isomer, or a combination thereof. 
     
     
         4 . The phospholipid microbubble of  claim 3 , wherein said omega-3 PUFA is selected from eicosapentaenoic acid (“EPA”), docosahexaenoic acid (“DHA”), or a combination thereof. 
     
     
         5 . The phospholipid microbubble of  claim 3 , wherein said omega-3 PUFA precursor is an □-linolenic acid. 
     
     
         6 . The phospholipid microbubble of  claim 3 , wherein said omega-3 PUFA-derived metabolite is selected from a resolvin, a neuroprotectin, a lipoxin, a neuroprostane, or a combination thereof. 
     
     
         7 . The phospholipid microbubble of  claim 1 , wherein said paramagnetic gas is selected from a perfluorocarbon compound, xenon, or hyperpolarized xenon. 
     
     
         8 . The phospholipid microbubble of  claim 1 , wherein said phospholipid microbubble in a micellar form or a liposomal form. 
     
     
         9 . The phospholipid microbubble of  claim 1 , wherein said plurality of PUFA-containing phospholipids comprises at least one PS-DHA phospholipid, PS-EPA phospholipid, PC-DHA phospholipid, or PC-EPA phospholipid. 
     
     
         10 . The phospholipid microbubble of  claim 1 , wherein said phospholipid microbubble further comprises a drug, a fat-soluble compound, an antioxidant, an antibody or a fragment thereof, or a specific ligand is conjugated to said phospholipid microbubble. 
     
     
         11 . A method of delivering a prophylactically or therapeutically effective amount of PUFA to an area of disease or injury in a subject, comprising the steps of:
 administering to said subject a plurality of phospholipid microbubbles which comprises a shell comprising a plurality of PUFA-containing phospholipids, and a core of paramagnetic gas surrounded by said shell comprising said plurality of PUFA-containing phospholipids;   allowing said phospholipid microbubbles to reach said area of disease or injury; and   applying ultrasound to said area of disease or injury to explode said phospholipid microbubbles.   
     
     
         12 . The method of  claim 11 , wherein said area of disease or injury is the heart. 
     
     
         13 . The method of  claim 11 , wherein said plurality of phospholipid microbubbles comprises a micellar form of said phospholipid microbubbles, a liposomal form of phospholipid microbubbles, or a combination thereof. 
     
     
         14 . A method of preventing or treating a disease in a subject, comprising the steps of:
 administering to said subject a prophylatically or therapeutic effective amount of a plurality of phospholipid microbubbles which comprises a shell comprising a plurality of PUFA-containing phospholipids, and a core of paramagnetic gas surrounded by said shell comprising said plurality of PUFA-containing phospholipids; and   applying ultrasound to said phospholipid microbubbles to explode said phospholipid microbubbles in said subject.   
     
     
         15 . The method of  claim 14 , wherein said disease is lupus erythematosis, multiple sclerosis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, diabetes mellitus, prostate cancer, breast cancer, depression, Alzheimer's disease or myocardial infarction. 
     
     
         16 . The method of  claim 14 , wherein said administration is a single intravenous administration of said plurality of phospholipid microbubbles. 
     
     
         17 . The method of  claim 14 , wherein said plurality of PUFA-containing phospholipids comprising at least one PS-DHA phospholipid, PS-EPA phospholipid, PC-DHA phospholipid, or PC-EPA phospholipid. 
     
     
         18 . The method of  claim 14 , wherein said plurality of phospholipid microbubbles comprises a micellar form of said phospholipid microbubbles, a liposomal form of said phospholipid microbubbles, or a combination thereof. 
     
     
         19 . The method of  claim 14 , wherein said administration is a co-administration of a micellar form of said phospholipid microbubbles and a liposomal form of said phospholipid microbubbles. 
     
     
         20 . The method of  claim 19 , wherein said co-administration is simultaneous, concurrent or sequential administration of said micellar form of said phospholipid microbubbles and said liposomal form of said phospholipid microbubbles.