Compositions and methods for producing emulsions for nuclear magnetic resonance techniques and other applications

Abstract

The disclosure provides, in part, compositions and methods for producing emulsions. In certain embodiments, emulsions of the disclosure can be used for the detection of inflammation and cell tracking using MRI. The disclosure provides, in part, methods for labeling, detecting and quantifying cell numbers in vivo. In certain embodiments, emulsions can be used as an artificial blood substitute

1 . An aqueous composition comprising perfluoro-15-crown-5 ether or PFPE oxide, an emulsifier, a surfactant co-mixture, and an additive. 
     
     
         2 . The aqueous composition of  claim 1 , wherein the emulsifier is also a non-ionic solubiliser. 
     
     
         3 . The aqueous composition of  claim 1 , wherein the emulsifier comprises glycerol polyethylene glycol ricinoleate. 
     
     
         4 . The aqueous composition of  claim 1 , wherein the surfactant co-mixture comprises 70 mol % lecithin, 28 mol % cholesterol, and 2 mol % DPPE. 
     
     
         5 . The aqueous composition of  claim 1 , wherein the additive is propylene glycol. 
     
     
         6 - 19 . (canceled) 
     
     
         20 . An aqueous composition comprising perfluoro-15-crown-5 ether in 35.6% w/v, an emulsifier in 3.0% w/v, a surfactant co-mixture in 2.0% w/v, wherein the surfactant co-mixture comprises lecithin, cholesterol, and DPPE, and an additive in 2.0% w/v, wherein the additive is propylene glycol. 
     
     
         21 . An aqueous composition comprising PFPE oxide in 35.6% w/v, an emulsifier in 3.0% w/v, a surfactant co-mixture in 2.0% w/v, wherein the surfactant co-mixture comprises lecithin, cholesterol, and DPPE, and an additive in 2.0% w/v, wherein the additive is propylene glycol. 
     
     
         22 - 23 . (canceled) 
     
     
         24 . An aqueous composition comprising perfluoro-15-crown-5 ether and a block copolymer, wherein the composition comprises perfluoro-15-crown-5 ether in the range of 10% to 20% w/w, and wherein the composition comprises the block copolymer in the range of 0.1% to 2.0% w/w. 
     
     
         25 . The aqueous composition of  claim 24 , wherein the block copolymer is poly(ethylene oxide)-polypropylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) tri-block copolymer comprising 80% PEO content. 
     
     
         26 - 29 . (canceled) 
     
     
         30 . An aqueous composition comprising perfluoro-15-crown-5 ether in 15% w/w and a block copolymer in 0.6% w/w. 
     
     
         31 . The aqueous composition of  claim 30 , wherein the block copolymer is poly(ethylene oxide)-polypropylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) tri-block copolymer comprising 80% PEO content. 
     
     
         32 - 35 . (canceled) 
     
     
         36 . An emulsion comprising a composition of  claim 1 . 
     
     
         37 - 39 . (canceled) 
     
     
         40 . A method for preparing an emulsion of  claim 36  comprising high energy methods. 
     
     
         41 - 42 . (canceled) 
     
     
         43 . A method for labeling a cell, the method comprising contacting the cell ex vivo with an emulsion of  claim 36  under conditions such that the fluorocarbon imaging reagent becomes associated with the cell. 
     
     
         44 . A method for detecting a cell in a subject, the method comprising:
 a) administering to the subject a cell that is labeled with an emulsion of  claim 36 ; and   b) examining at least a portion of the subject by a nuclear magnetic resonance technique, thereby detecting a labeled cell in the subject.   
     
     
         45 . A method for detecting transplanted cells in a transplant recipient, the method comprising:
 a) administering cells for transplant to a transplant recipient, at least a portion of which cells for transplant are labeled with an emulsion of  claim 36 ;   b) examining at least a portion of the subject by a nuclear magnetic resonance technique, thereby detecting the labeled cells.   
     
     
         46 . A method for quantifying cell number in vivo, the method comprising:
 a) administering to the subject cells that are labeled with an emulsion of  claim 36 ;   b) examining at least a portion of the subject by a nuclear magnetic resonance technique, thereby detecting labeled cells in the subject; and   c) quantifying the number of labeled cells in a region of interest (ROI).   
     
     
         47 . A method for quantifying leukocyte number in vivo, the method comprising:
 a) administering to the subject an emulsion of  claim 36 ;   b) extravesating a sample of peripheral blood from the subject and measure the effective cell loading of leukocytes;   c) examining at least a portion of the subject by a nuclear magnetic resonance technique, thereby detecting labeled cells in the subject; and   d) quantifying the number of labeled cells in a region of interest (ROI).   
     
     
         48 . (canceled) 
     
     
         49 . A method for labeling a cell, the method comprising contacting the cell in vivo with an emulsion of  claim 36  under conditions such that the fluorocarbon imaging reagent becomes associated with the cell. 
     
     
         50 . A method for detecting a cell in a subject, the method comprising:
 a) administering to the subject an emulsion of  claim 36 ; and   b) examining at least a portion of the subject by a nuclear magnetic resonance technique, thereby detecting a labeled cell in the subject.   
     
     
         51 . A method for measuring the partial pressure of oxygen in a tissue, the method comprising contacting the tissue in vivo with an emulsion of  claim 36  under conditions such that the fluorocarbon imaging reagent becomes associated with the tissue. 
     
     
         52 . A method for detecting elevated vascular permeability in a tissue, the method comprising contacting the tissue in vivo with an emulsion of  claim 36  under conditions such that the fluorocarbon imaging reagent becomes associated with the tissue. 
     
     
         53 . A method for detecting inflamation in a tissue, the method comprising contacting the tissue in vivo with an emulsion of  claim 36  under conditions such that the fluorocarbon imaging reagent becomes associated with the tissue. 
     
     
         54 . A labeled cellular formulation for administration to a subject, the formulation comprising:
 a) a cell; and   b) an emulsion of  claim 36  that is associated with the cell.