Inhibition of neovascularization by cerium oxide nanoparticles

• US 8,703,200 B2
• Filed: 04/24/2009
• Issued: 04/22/2014
• Est. Priority Date: 04/29/2005
• Status: Active Grant

• Current Assignee: University of Central Florida Research Foundation Inc. (State University System of Florida)
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: McGinnis, James F., Zhou, Xiaohong, Wong, Lily L., Seal, Sudipta
• Primary Examiner(s): Justice, Gina C
• Assistant Examiner(s): Alley, Genevieve S
• Application Number:
  US12/429,650
• Publication Number:
  US 20090269410A1
• Time in Patent Office: 1,824 Days
• Field of Search: 424/489, 424/617
• US Class Current: 424/489
• CPC Class Codes: A61K 33/244 Lanthanides; Compounds thereof medicinal preparations containing radioactive lanthanides for use in therapy or testing in vivo A61K51/00
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

The present invention provides methods for reducing, reversing or inhibiting neovascularization in a tissue of a mammalian subject having a pathological condition involving neovascularization by administration in vivo of nanoceria particles (cerium oxide nanoparticles) to the subject. The method of the invention is useful, for example, for reducing, treating, reversing or inhibiting neovascularization in ocular tissue such as the retina, macula or cornea; in skin; in synovial tissue; in intestinal tissue; or in bone. In addition, the method of the invention is useful for reducing or inhibiting neovascularization in a neoplasm (tumors), which can be benign or malignant and, where malignant, can be a metastatic neoplasm. As such, the invention provides compositions, which contain nanoceria particles and are useful for reducing, treating, reversing or inhibiting angiogenesis in a mammalian subject.

Claims

1. A method of inhibiting, reducing and/or reversing neovascularization associated with a pathological ocular condition in a mammalian subject, the method comprising the steps of:

administering a therapeutically effective amount of a pharmaceutical composition to a mammalian subject exhibiting neovascularization associated with a pathological ocular condition, the pharmaceutical composition comprising cerium oxide nanoparticles and a pharmaceutically acceptable carrier; and

reducing at least one of (a) at least one vascular anomaly, (b) the number of illicit neovessels, (c) the rate of retinal neovascularization, and (d) the rate of proliferation of neovascular tissue in the eye of the mammalian subject upon administration of the cerium oxide nanoparticles present in the pharmaceutical composition.

2. The method of claim 1, wherein the at least one vascular anomaly, the number of illicit neovessels, the rate of retinal neovascularization, and/or the rate of proliferation of neovascular tissue in the eye of the mammalian subject is substantially reduced to 25% or less of that observed in the absence of administration of the pharmaceutical composition.

3. The method of claim 1, wherein the at least one vascular anomaly, the number of illicit neovessels, the rate of retinal neovascularization, and/or the rate of proliferation of neovascular tissue in the eye of the mammalian subject is substantially reduced to 10% or less of that observed in the absence of administration of the pharmaceutical composition.

4. The method of claim 1, wherein the at least one vascular anomaly is selected from the group consisting of retinal neovascular lesions, choroidal neovascular lesions, choroidal neovascular tufts, retinal neovascular blebs, and combinations thereof.

5. The method of claim 1, wherein the pathological ocular condition having neovascularization associated therewith is at least one of age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, retinal detachment, inherited retinal degeneration, Stargardt'"'"'s disease, and occlusive retinopathy.

6. The method of claim 1, wherein the cerium oxide nanoparticles have a size in a range of from about 1 nanometer in diameter to about 10 nanometers in diameter.

7. The method of claim 1, wherein the cerium oxide nanoparticles have a size in a range of from about 1 nanometer in diameter to about 7 nanometers in diameter.

8. The method of claim 1, wherein the cerium oxide nanoparticles are present in the pharmaceutical composition at a concentration in a range of from about 1 nM to about 1.0 mM.

9. The method of claim 1, wherein the cerium oxide nanoparticles are present in the pharmaceutical composition at a concentration in a range of from about 1 nM to about 50 nM.

10. A method of treating a mammalian subject having at least one neovascular lesion in an eye thereof, the method comprising the steps of:

administering a therapeutically effective amount of a pharmaceutical composition to the eye of the mammalian subject, the pharmaceutical composition comprising cerium oxide nanoparticles and a pharmaceutically acceptable carrier, wherein the cerium oxide nanoparticles have a size in a range of from about 1 nanometer in diameter to about 10 nanometers in diameter and are present in the pharmaceutical composition at a concentration in a range of from about 1 nM to about 1.0 mM; and

reducing the at least one neovascular lesion in the eye of the mammalian subject to 50% or less of that observed in the absence of administration of the pharmaceutical composition, and wherein the at least one neovascular lesion is at least one of a retinal neovascular lesion and a choroidal neovascular lesion.