Nanoparticles for protein drug delivery
View Patent ↗The invention discloses the nanoparticles composed of chitosan, poly-glutamic acid, and at least one antineoplastic drug or cancer therapeutic agent characterized with a positive surface charge and their enhanced permeability for paracellular drug and bioactive agent delivery.
1. A method of treating a cancer in an animal subject comprising administering nanoparticles consisting of an antineoplastic drug or anti-cancer therapeutic agent in effective amount to treat said cancer, positively charged chitosan, and a negatively charged substrate, wherein a surface of said nanoparticles is dominated by the positively charged chitosan.
2. The method of claim 1 , wherein said anti-cancer therapeutic agent is pemetrexed.
3. The method of claim 1 , wherein said anti-cancer therapeutic agent is gemcitabine.
4. The method of claim 1 , wherein said anti-cancer therapeutic agent is selected from the group consisting of alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors, and antitumor agents.
5. The method of claim 1 , wherein the chitosan has a molecular weight about 80 kDa or less.
6. The method of claim 1 , wherein said negatively charged substrate is selected from the group consisting of γ-PGA, α-PGA, derivatives of PGA, salts of PGA, and combinations thereof.
7. The method of claim 1 , wherein said nanoparticles have a mean particle size between about 50 and 400 nanometers.
8. The method of claim 1 , wherein the chitosan is N-trimethyl chitosan, EDTA-chitosan, or chitosan derivatives.
9. The method of claim 1 , wherein said nanoparticles further comprise a permeation enhancer.
10. The method of claim 9 , wherein said permeation enhancer is selected from the group consisting of Ca 2+ chelators, bile salts, anionic surfactants, medium-chain fatty acids, phosphate esters, and chitosan derivatives.
11. The method of claim 1 , wherein said nanoparticles are freeze-dried, thereby said nanoparticles being in a powder form.
12. The method of claim 1 , wherein said nanoparticles are mixed with trehalose and then freeze-dried, thereby said nanoparticles being in a powder form.
13. The method of claim 1 , wherein said nanoparticles are formed via a simple and mild ionic-gelation method.
14. The method of claim 1 , wherein said nanoparticles further comprise zinc, magnesium sulfate or sodium tripolyphosphate (TPP).
15. The method of claim 1 , wherein at least a portion of said nanoparticles is crosslinked.
16. The method of claim 1 , wherein said nanoparticles are loaded in capsules or tablets.
17. The method of claim 16 , wherein said capsules are treated with an enteric coating.
18. The method of claim 16 , wherein said capsules further comprise at least one permeation enhancer.
19. The method of claim 16 , wherein said capsules further comprise a solubilizer or pharmacopoeial excipients.
20. The method of claim 1 , wherein said anti-cancer therapeutic agent is a monoclonal antibody or a tyrosine kinase inhibitor.