Nanoparticles for drug delivery
View Patent ↗The invention discloses the nanoparticles composed of chitosan, poly-glutamic acid, and at least one bioactive agent for treating wet AMD. The nanoparticles are characterized with a positive surface charge and their enhanced permeability for paracellular drug delivery.
1. A method of treating a patient with a potential risk of blood clot formation, comprising administering nanoparticles to said patient orally, said nanoparticles having a composition comprising a shell component and a core component, wherein the shell component comprises chitosan and wherein the core component is consisted of said chitosan, a negatively charged compound that is conjugated to said chitosan, and an anti-clotting compound.
2. The method of claim 1 , wherein the blood clot formation is deep vein thrombosis or pulmonary embolism.
3. The method of claim 1 , wherein the blood clot formation is formed after a surgical procedure in the patient.
4. The method of claim 1 , wherein said negatively charged compound is polyglutamic acid or a derivative of said polyglutamic acid.
5. The method of claim 1 , wherein said negatively charged compound is poly(α-glutamic acid), poly(γ-glutamic acid) or a salt of polyglutamic acids.
6. The method of claim 1 , wherein said anti-clotting compound is heparin or heparan sulfate.
7. The method of claim 6 , wherein said heparin is low molecular weight heparin.
8. The method of claim 1 , wherein said anti-clotting compound is hirudin, coumadin, or coumadin-like compounds.
9. The method of claim 1 , wherein said anti-clotting compound is warfarin.
10. The method of claim 1 , wherein the nanoparticles have a mean particle size between about 50 and 400 nanometers.
11. The method of claim 1 , wherein said nanoparticles are further encapsulated.
12. The method of claim 1 , wherein said chitosan is low molecular weight chitosan.
13. The method of claim 1 , wherein said chitosan is low molecular weight chitosan with a molecular weight of 80 kDa or less.
14. The method of claim 1 , wherein said negatively charged compound is glycosaminoglycan.
15. The method of claim 1 , wherein said negatively charged compound is heparin.
16. The method of claim 4 , wherein the derivative of said polyglutamic acid is selected from the group consisting of poly-L-glutamic acid, poly-D-glutamic acid, poly-L-α-glutamic acid, poly-γ-D-glutamic acid, poly-γ-DL-glutamic acid, and polyethylene glycol (PEG) derivatives of polyglutamic acid.
17. The method of claim 7 , wherein the low molecular weight heparin is dalteparin, cnoxaparin or tinzaparin.
18. The method of claim 1 , wherein said nanoparticles are prepared using a simple and mild ionic-gelation method.
19. The method of claim 1 , wherein said chitosan is trimethyl chitosan.
20. The method of claim 1 , wherein the nanoparticles are crosslinked with a crosslinking agent or with ultraviolet irradiation.