NANOFORMULATION OF VITAMIN D DERIVATIVES AND/OR VITAMIN D METABOLITES

• US 20130149385A1
• Filed: 12/06/2012
• Published: 06/13/2013
• Est. Priority Date: 12/09/2011
• Status: Active Grant

• Current Assignee: Shaker A. Mousa
• Original Assignee: Shaker A. Mousa
• Inventors: Mousa, Shaker A.
• Granted Patent: US 8,968,790 B2
• Time in Patent Office: Days
• US Class Current: 424/493
• CPC Class Codes: A61K 47/542 Carboxylic acids, e.g. a fatty acid or an amino acid
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/906 Drug delivery

Abstract

A nanoformulation that includes loaded nanoparticles. Each nanoparticle includes a modified chitosan polymer encapsulating at least one vitamin D derivative, at least one vitamin D metabolite, or combinations thereof. The modified chitosan polymer includes chitosan covalently linked to at least one entity selected from the group consisting of fatty acids (omega-3-fattay acids), amino acids, deoxycholic acid, alginate, arginine-alginate, hyaluronic acid, collagen, collagen-hydroxyapatite, poly(lactic-co-glycolic acid) (PLGA), and combinations thereof. A structure includes a medium and the nanoformulation, wherein the nanoparticles are dispersed in the medium. A method of using the nanoformulation to treat a disorder and improve efficacy of current therapies where resistance develop in a patient includes administering to the patient a therapeutically effective amount of the nanoformulation for treating the disorder. A nano-cosmetic formulation, comprising a cosmetic includes the nanoformulation, wherein the modified chitosan polymer encapsulates the at least one vitamin D derivative, and wherein the at least one vitamin D derivative encompasses 0.1 to 20.0 wt % of the nano-cosmetic formulation'"'"'s total weight.

Claims

1. A nanoformulation, comprising:

nanoparticles, each nanoparticle comprising a modified chitosan polymer encapsulating at least one vitamin D derivative, at least one vitamin D metabolite, or combinations thereof,

wherein the modified chitosan polymer comprises chitosan covalently linked to at least one entity selected from the group consisting of fatty acids, amino acids, deoxycholate, alginate, arginine-alginate, collagen, collagen-hydroxyapatite, poly(lactic-co-glycolic acid) (PLGA), and combinations thereof.

2. The nanoformulation of claim 1, wherein the modified chitosan polymer is hydrophobic.

3. The nanoformulation of claim 1, wherein the modified chitosan polymer comprises chitosan covalently linked to the fatty acids, and wherein the fatty acids are selected from the group consisting of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linolenic acid, hyaluronic acid, and combinations thereof.

4. The nanoformulation of claim 1, wherein the modified chitosan polymer encapsulates the at least one vitamin D derivative, and wherein the at least one vitamin D derivative is selected from the group consisting of vitamin D1 (ergocalciferol with lumisterol in a 1:

1 ratio), vitamin D2 (ergocalciferol), D3 (cholecalciferol), D4 (22-dihydroergocalciferol), D5 (sitocalciferol), pre-vitamin D2, pre-vitamin D3, ergosterol, 7-dehydrocholesterol, lumisterol, pyrocalciferol, isopyrocalciferol, tachysterol, calcipotriene, calcitriol, and combination thereof.

5. The nanoformulation of claim 1, wherein the modified chitosan polymer encapsulates the at least one vitamin D metabolite, and wherein the at least one vitamin D metabolite is selected from the group consisting of 25 hydroxyvitamin D, (1, 25 hydroxyvitamin D), and combinations thereof.

6. The nanoformulation of claim 1, wherein the chitosan is covalently linked to the at least one entity by a respective cleavable linker.

7. The nanoformulation of claim 6, wherein the respective cleavable linker cleavably links a NH₂ group or a CH₂OH group in the chitosan to an entity of the at least one entity.

8. The nanoformulation of claim 1, wherein the chitosan comprises a molecular weight in a range of 5 to 150 kilo Daltons.

9. The nanoformulation of claim 1, wherein the nanoformulation is configured to be applied topically or delivered orally to a mammal.

10. The nanoformulation of claim 9, wherein the modified chitosan polymer has muco-adhesive properties with respect to the mammal.

11. The nanoformulation of claim 1, wherein the modified chitosan polymer encapsulates at least one antioxidant selected from the group consisting of a polyphenol, an isoflavone, a flavone, and combinations thereof.

12. A structure, comprising:

a medium; and

the nanoformulation of claim 1, wherein the nanoparticles are dispersed in the medium.

13. The structure of claim 12, wherein the medium is selected from the group consisting of polyethylene glycol (PEG), poly oxy ethylene-glyceryl-tri-fatty acids (POEG), water resistant thin film forming cellulose polymer bridged by ethyl or ethoxy ether linkage, and silicone gel.

14. The structure of claim 13, wherein the modified chitosan polymer encapsulates at least one vitamin D derivative, and wherein the at least one vitamin D derivative has a concentration of 0.01-10 mg/ml in the medium.

15. The structure of claim 12, wherein the medium is selected from the group consisting of a tablet, a capsule, and an emulsion, wherein the modified chitosan polymer encapsulates at least one vitamin D derivative, and wherein the at least one vitamin D derivative has a concentration of 0.01-10 mg/ml in the medium.

16. The structure of claim 12, wherein the nanoparticles are selected from the group consisting of eicosapentaenoic acid (EPA) nanoparticles, docosahexaenoic acid (DHA) nanoparticles, chitosan-deoxycholate nanoparticles, chitosan-alginate nanoparticles, chitosan-arginine-alginate nanoparticles, chitosan-linolenic acid nanoparticles, chitosan-hyaluronic acid nanoparticles, chitosan-collagen-hydroxyapatite nanoparticles, chitosan-poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and combinations thereof.

17. A method of using a nanoformulation to treat a disorder in a patient, said method comprising:

administering to the patient a therapeutically effective amount of the nanoformulation of claim 1 for treating the disorder.

18. The method of claim 17, wherein the disorder, is selected from the group consisting of osteoporosis, skin aging, psoriasis, a vascular disorder, cardiovascular, cancer, and infectious disorders.

19. The method of claim 17, wherein said administering comprises applying the nanoformulation topically to the patient or delivering the nanoformulation orally to the patient.

20. A nano-cosmetic formulation, comprising a cosmetic that includes the nanoformulation of claim 1, wherein the modified chitosan polymer encapsulates at least one vitamin D derivative, and wherein the at least one vitamin D derivative encompasses 0.1 to 20.0 wt % of the total weight of the nano-cosmetic formulation.

21. The nano-cosmetic formulation of claim 20, wherein the cosmetic is in a form of cream, ointment, shampoo, or rinse.

22. A method of improving the response of a patient to a therapy used to treat the patient for a disorder, said method comprising:

administering the nanoformulation of claim 1 systemically to the patient to counteract resistance developed by the patient to the therapy.

23. The method of claim 22, wherein the disorder is selected from the group consisting of cancer, viral infection, hepatitis B, hepatitis C, diabetes, and combinations thereof.