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|Title:||Methods for delivering compounds into a cell|
|Abstract:||The present invention is directed, inter alia, to a method for delivering a compound into a cell comprising administering to the cell the compound to be delivered, an organic halide, and/or a carrier. Ultrasound may also be applied, if desired.|
|Inventor(s):||Unger; Evan C. (Tucson, AZ), McCreery; Thomas (Tucson, AZ)|
|Assignee:||ImaRx Pharmaceutical Corp. (Tucson, AZ)|
|Filing Date:||Mar 18, 2004|
|Claims:||1. A method for delivering a protein into a cell in vivo, comprising: (a) forming a plurality of protein-halide vesicles comprising the protein to be delivered and an organic halide incorporated in the core of the vesicles; and (b) administering the protein-halide vesicles to the cell, wherein the organic halide is selected from the group consisting of 1-bromo-nonafluorobutane, perfluorooctyliodide, perfluoroocytlbromide, 1-chloro-1-fluoro-1-bromomethane, 1,1,1-trichloro-2,2,2-trifluoroethane, 1,2-dichloro-2,2-difluoroethane, 1,1-dichloro-1,2-difluoroethane, 1,2-dichloro-1,1,3-trifluoropropane, 1-bromoperfluorobutane, 2-iodo-1,1,1-trifluoroethane, 5-bromovaleryl chloride, 1,3-dichlorotetrafluoroacetone, 1-bromo-1,1,2,3,3,3-hexafluoropropane, 2-chloro-1,1,1,4,4,4-hexafluoro-2-butene, 2-chloropentafluoro-1,3-butadiene, iodotrifluoroethylene, 1,1,2-trifluoro-2-chloroethane, 1,2-difluorochloroethane, 1,1-difluoro-2-chloroethane, 1,1-dichlorofluoroethane, heptafluoro-2-iodopropane, bromotrifluoroethane, chlorotrifluoromethane, dibromofluoromethane, chloropentafluoroethane, bromochlorodifluoromethane, dichloro-1,1,2,2-tetrafluoroethane, 1,1,1,3,3-pentafluoropentane, perfluorotributylamine, perfluorotripropylamine, 2,2,2-trifluoroethylacrylate, 3-(trifluoromethoxy)-acetophenone, 1,1,2,2,3,3,4,4-octafluorobutane, 1,1,1,3,3-pentafluorobutane, 1-fluorobutane, 1,1,2,2,3,3,4,4-octafluorobutane, 1,1,1,3,3-pentafluorobutane, tetradecaperfluoroheptane, dodecaperfluorocyclohexane, perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane, perfluoropentane, perfluorohexane, perfluoroheptane, perfluorooctane, perfluorononane, perfluorodecane, perfluorododecane, perfluoro-2-methyl-2-pentene, perfluorocyclohexane, perfluoropropylene, perfluorocyclobutane, perfluoro-2-butyne, perfluoro-2-butene, perfluorobuta-1,3-diene, perfluorobutylethyl ether, bis(perfluoroisopropyl) ether, bis(perfluoropropyl) ether, perfluoromethyl tetrahydrofuran, perfluoro t-butyl methyl ether, perfluoro isobutyl methyl ether; perfluoro n-butyl methyl ether, perfluoro isopropyl ethyl ether, perfluoro n-propyl ethyl ether, perfluoro cyclobutyl methyl ether, perfluoro cyclopropyl ethyl ether, perfluoro isopropyl methyl ether, perfluoro n-propyl methyl ether, perfluoro diethyl ether, perfluoro cyclopropyl methyl ether, perfluoro methyl ethyl ether, and perfluoro dimethyl ether, wherein the path of administering of the protein-halide composition to the cell is selected from a group consisting of the administering through a cell membrane, cell wall, and nuclear membrane, or any combination thereof, to achieve the intracellular delivery of the protein thereby. |
2. The method of claim 1, wherein the organic halide is selected from the group consisting of 1-bromo-nonafluorobutane, 1,1,1,3,3-pentafluoropentane, perfluorohexane, perfluorocyclohexane, 1-bromo-1,1,2,3,3,3-hexafluoropropane, heptafluoro-2-iodopropane, 1,1,2,2,3,3,4,4-octafluorobutane, 1-fluorobutane, tetradecaperfluoroheptane, and dodecaperfluorocyclohexane.
3. The method of claim 1, wherein the organic halide is selected from the group consisting of perfluorohexane and perfluorocyclohexane.
4. The method of claim 1, wherein the protein is selected from the group consisting of albumin, collagen, polyarginine, polylysine, polyhistidine, .gamma.-globulin, and .beta.-globulin.
5. The method of claim 1, wherein the protein is a cationic protein.
6. The method of claim 5, wherein the cationic protein is selected from the group consisting of polylysine and polyethyleneimine.
7. The method of claim 1, further comprising applying ultrasound to the cell.
8. The method of claim 7, wherein the ultrasound is applied at a frequency between about 40 kHz and 25 MHz, and an energy level between about 500 mW/cm.sup.2 and 10 W/cm.sup.2.
9. The method of claim 7, wherein the ultrasound is applied at a frequency between about 200 kHz and 500 kHz, and the energy level is between about 200 mW/cm.sup.2 and 500 W/cm.sup.2.
10. The method of claim 7, wherein the ultrasound is applied at a frequency between about 1 MHz and 20 MHz, and the energy level is between about 100 W/cm.sup.2 and 200 W/cm.sup.2.
11. The method of claim 10, wherein the ultrasound is applied at a duty cycle between about 1% and 100% of the treatment time.
12. The method of claim 7, wherein the protein and the ultrasound are administered and applied simultaneously.