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|Title:||Compositions and methods for nucleic acid delivery to the lung|
|Abstract:||A dry powder composition comprises nucleic acid constructs dispersed within with a hydrophilic excipient material, where the powder particles have an average size in the range from 0.5 .mu.m to 50 .mu.m. Nucleic acid constructs may comprise bare nucleic acid molecules, viral vectors, or vesicle structures. The hydrophilic excipient material will be selected to stabilize the nucleic acid molecules in the constructs, enhance dispersion of the nucleic acid in dry powder aerosols, and enhance wetting of the nucleic acid constructs as they are delivered to moist target locations within the body.|
|Inventor(s):||Eljamal; Mohammed (San Jose, CA), Patton; John S. (San Carlos, CA), Foster; Linda (Sunnyvale, CA), Platz; Robert M. (Half Moon Bay, CA)|
|Assignee:||Inhale Therapeutic Systems, Inc. (San Carlos, CA)|
|Filing Date:||Oct 26, 1999|
|Claims:||1. A spray dried powder composition comprising a nucleic acid construct dispersed in a hydrophilic excipient. |
2. A dry powder composition comprising a nucleic acid construct dispersed in a hydrophilic excipient.
3. A method for preparing the dry powder composition of claim 2, said method comprising:
(a) suspending a nucleic acid construct in an aqueous solution of an excipient to form a suspension; and
(b) spraying droplets of the suspension into a heated gas stream to form a dry powder comprising the nucleic acid construct dispersed within the hydrophilic excipient.
4. The method of claim 3, wherein said heated gas stream is at a temperature ranging from about 50.degree. C. to 150.degree. C.
5. The method of claim 3, wherein the weight ratio of nucleic acid construct to hydrophilic excipient in the initial suspension is from 1:1 to 1:10.
6. A dry powder composition produced by the method of claim 3.
7. The composition of claim 1 or claim 2, wherein said nucleic acid construct comprises bare nucleic acid molecules.
8. The composition of claim 1 or claim 2, wherein said nucleic acid construct comprises nucleic acid molecules present in a delivery vehicle.
9. The composition of claim 8, wherein said delivery vehicle comprises liposomal vesicles.
10. The composition of claim 9, wherein the liposomal vesicles comprise anionic liposomes.
11. The composition of claim 1 or claim 2, wherein said nucleic acid construct comprises a structural gene operably linked to a regulatory region.
12. The composition of claim 1 or claim 2 comprising dry powder particles, wherein the nucleic acid construct is present in the particles at a weight ratio from 1:10 to 1:500 (nucleic acid construct: particle).
13. The composition of claim 1 or claim 2, wherein said nucleic acid construct comprises plasmid DNA.
14. The composition of claim 1 or claim 2, wherein said excipient is selected from the group consisting of proteins, peptides, carbohydrates, amino acids, organic acids and their salts, and inorganic salts.
15. The composition of claim 14, wherein said excipient is serum albumin.
16. The composition of claim 1 or claim 2, wherein said powder is characterized by a dispersibility of at least about 36%.
17. The composition of claim 1 or claim 2 comprising particles having an average particle size in the range from 0.5 microns to 50 microns.
18. The composition of claim 1 or claim 2 comprising particles having a mass median aerodynamic diameter (MMAD) of less than 5 microns.
19. A method for delivery of a nucleic acid construct to the lungs of a human patient, said method comprising administering by inhalation the composition of claim 1 or claim 2 in aerosolized form.
20. A method for delivering a nucleic acid dry powder composition to a patient, said method comprising:
dispersing an amount of the powder composition of claim 1 or claim 2 in a gas stream to form an aerosol, and delivering the aerosol to the lungs of said patient by inhalation.
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