Compositions and methods for diagnosing or treating neutrophil-mediated inflammatory disease
Disclosed are nanoparticle compositions comprising nanoparticles prepared from denatured, cross-linked albumin and a therapeutic agent for treating a neutrophil-mediated inflammation, and methods of treating neutrophil-mediated inflammation using the compositions.
1. A method of treating a neutrophil-mediated inflammatory disease in a subject in need of treatment comprising:
administering to the subject a therapeutically effective amount of a composition comprising nanoparticles, each nanoparticle consisting of denatured, cross-linked albumin and a therapeutic agent, the nanoparticles selectively binding to and internalized by activated neutrophils.
2. The method of claim 1 , wherein the therapeutic agent is one or more selected from the group consisting of anti-inflammatory glucocorticoids, NF-kB inhibitors, p38MAP kinase inhibitors, Syk/Zap kinase inhibitors and siRNA oligonucleotides.
3. The method of claim 1 , wherein the therapeutic agent is dexamethasone or piceatannol.
4. The method of claim 1 , wherein the neutrophil-mediated inflammatory disease is selected from the group consisting of sepsis, myocardial infarction, acute lung injury, stroke and ischemia-reperfusion injury.
5. The method of claim 1 , wherein the therapeutic agent is loaded within the nanoparticles or covalently conjugated to the albumin.
6. The method of claim 1 , wherein each of the nanoparticles has a mean particle diameter of about 90 nm to about 110 nm.
7. The method of claim 1 , wherein the nanoparticles are administered intravenously.
8. The method of claim 1 , wherein the subject is a human.
9. The method of claim 1 wherein the denatured albumin is denatured by desolvation.
10. The method of claim 9 wherein the albumin is desolvated by treatment with ethanol.
11. The method of claim 1 wherein the albumin is bovine serum albumin.
12. The method of claim 1 wherein the albumin is cross-linked with glutaraldehyde.
13. A composition comprising nanoparticles, each nanoparticle consisting of denatured, cross-linked albumin and a therapeutic agent, the nanoparticles selectively binding to and internalized by activated neutrophils.