Nanoparticle and Polymer Formulations for Thyroid Hormone Analogs, Antagonists, and Formulations and Uses Thereof

• US 20110142941A1
• Filed: 11/16/2010
• Published: 06/16/2011
• Est. Priority Date: 12/22/2006
• Status: Active Grant

• Current Assignee: NanoPharmaceuticals LLC
• Original Assignee: NanoPharmaceuticals LLC
• Inventors: Davis, Paul J., Mousa, Shaker A.
• Granted Patent: US 9,289,395 B2
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/6935 the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
• CPC Class Codes: A61K 47/6937 the polymer being PLGA, PLA or polyglycolic acid
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/14 for lactation disorders, e.g. galactorrhoea
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Disclosed are methods of treating subjects having conditions related to angiogenesis including administering an effective amount of a polymeric Nanoparticle form of thyroid hormone agonist, partial agonist or an antagonist thereof, to promote or inhibit angiogenesis in the subject. Compositions of the polymeric forms of thyroid hormone, or thyroid hormone analogs, are also disclosed.

Claims

1. A method of suppressing growth of cancer cells which are resistant to drug therapy, comprising administering to a subject in need thereof an amount of tetrac, triac, tetrac and triac nanoparticles or analogs thereof, effective for effective for suppressing the growth.

2. The method of claim 1, wherein said therapy-resistant cancer cells are selected from the group consisting of a primary or metastatic tumor, breast cancer, thyroid cancer, neuroblastoma, glioma and glioblastoma multiforme and other brain cancers, colon cancer, head-and-neck cancers, melanoma and basal cell and squamous cell carcinomas of the skin, sarcoma, ovarian cancer, prostate cancer, kidney cancer, hepatoma, lung cancer and stomach cancer.

3. The method of claim 1, wherein said drug therapy comprises administration of conventional or novel chemotherapeutic drugs.

4. The method of claim 3, wherein the chemotherapeutic drugs are selected from the group consisting of doxorubicin, etoposide, cyclophosphamide, 5-fluorouracil, cisplatin, trichostatin A, paclitaxel, gemcitabine, taxotere, cisplatinum, carboplatinum, irinotecan, topotecan, adriamycin, bortezomib and atoposide or novel derivatives of the foregoing agents.

5. The method of claim 1, further comprising administering a chemotherapeutic drug.

6. The method of claim 3, wherein the chemotherapeutic drugs are selected from the group consisting of doxorubicin, etoposide, cisplatin, and trichostatin A.

7. The method of claim 1, wherein the tetrac or tetrac analog is a nanoparticle conjugate comprising a nanoparticle conjugated to a plurality of tetrac particles with a particle size between 10 and 1000 nm, wherein the tetrac particles are bound to the nanoparticle by an ether (—

O—

) or sulfur (—

S—

) linkage bridging the alcohol moiety of the tetrac particles and the nanoparticle conjugation.

8. The method of claim 1, wherein the tetrac, tetrac nanoparticle or analog thereof is conjugated to a member selected from the group consisting of:

polyvinyl alcohol, acrylic acid ethylene co-polymer, polyethyleneglycol (PEG), polylactic acid, polyglycolide, polylactide, agarose, PEO, m-PEG, PVA, PLLA, PGA, Poly L-Lysine, Human Serum Albumin, Cellulose Derivative, Carbomethoxy/ethyl/hydroxypropyl, Hyaluronic Acid, Folate Linked Cyclodextrin/Dextran, Sarcosine/Amino Acid spaced Polymer, Alginate/Carrageenan, Pectin/Chitosan, Dextran, Collagen, Poly amine, Poly aniline, Poly alanine, Polytryptophan, poly(lactic-co-glycolic acid) (PLGA), and Polytyrosine.

9. The method of claim 7, wherein the tetrac or tetrac analog is a nanoparticle with a protecting group at the NH2 moiety.

10. The method of claim 9, wherein the protecting group is selected from the group consisting of N-Methyl, N-Ethyl, N-Triphenyl, N-Propyl, N-Isopropyl, N-tertiary butyl, and other functional groups.

11. The method of claim 7, wherein the nanoparticle contains between 1 and 100 tetrac or tetrac analog molecules per nanoparticle.

12. The method of claim 11, wherein the nanoparticle contains between 15 and 30 tetrac or tetrac analog molecules per nanoparticle.

13. The method of claim 12, wherein the nanoparticle contains between 20 and 25 tetrac or tetrac analog molecules per nanoparticle.

14. The method of claim 1, wherein the tetrac, tetrac analog or nanoparticle thereof is in a pharmaceutical formulation comprising a pharmaceutically acceptable carrier.

15. The method of claim 14, wherein the pharmaceutical formulation further comprises one or more pharmaceutically acceptable excipients.

16. The method of claim 15, wherein the formulation has a parenteral, oral, rectal, or topical mode of administration, or combinations thereof.

17. A method of increasing the chemosensitivity of cancer cells by administering to the cells tetrac, tetrac analogs, or nanoparticles thereof in an amount sufficient to enhance the chemosensitivity.

18. A method of treating a patient suffering from the presence of a tumor, comprising administering to said patient tetrac, tetrac analogs, or nanoparticles thereof in an amount effective for enhancing the chemosensitivity of cancer cells.