Iron chelators and use thereof for reducing transplant failure during rejection episodes
Formulations and methods are provided for improving the function, i.e. clinical outcome, of solid organ transplants. Lung transplantation is of particular interest. In the methods of the invention, a nanoparticle formulation comprising an effective dose of an iron chelator active agent in nanoparticle form, including without limitation, deferoxamine (DFO), deferasirox (DFX), and deferiprone (DFP), etc. is topically applied to the surface of tissues during episodes of graft rejection.
1. A method of improving clinical outcome in an individual following lung transplantation, the method comprising:
directly contacting a bronchial passage of the individual, in a rejection episode following transplantation, with an effective dose of a nanoparticle formulation comprising an effective dose of an iron chelating agent;
wherein ischemia and hypoxia at the contacted surface is reduced and clinical outcome is improved.
2. The method of claim 1 , wherein the contacting step is performed by pulmonary inhalation of an aerosol formulation.
3. The method of claim 2 , wherein the iron chelator is selected from deferoxamine (DFO), deferasirox (DFX), and deferiprone (DFP).
4. The method of claim 3 , wherein the iron chelator is DFO.
5. The method of claim 2 , wherein the nanoparticle is comprised of the iron chelating agent and a pharmaceutically acceptable stabilizer.
6. The method of claim 5 , wherein the iron chelator comprises from about 5% to about 75% of the total weight of the nanoparticle.
7. The method of claim 6 , wherein the iron chelator comprises from about 40% to about 60% of the total weight of the nanoparticle.
8. The method of claim 5 , wherein the stabilizer comprises cationic lipids.
9. The method of claim 5 , wherein the stabilizer comprises phospholipids.
10. The method of claim 5 , wherein the stabilizer comprises lecithin.
11. The method of claim 5 , wherein the stabilizer further comprises protein.
12. The method of claim 11 , wherein the stabilizer comprises a mixture of protein, and a cationic lipid in a ratio of from about 1:15 to 1:5 by weight.
13. The method of claim 5 , wherein the nanoparticles are formed by precipitation of the iron chelating agent and pharmaceutically acceptable stabilizer from a liquid suspension.
14. The method of claim 5 , wherein the nanoparticles have a diameter of from about 10 nm to about 5 μm.
15. The method of claim 14 , wherein the nanoparticles have a diameter of from about 100 nm to about 5 μm.
16. The method of claim 5 , wherein the nanoparticles are formulated by suspension in a physiologically acceptable carrier.
17. The method of claim 1 , wherein the formulation is provided in a container and carrier for generation of an aerosol.