Nanoparticles for protein drug delivery
View Patent ↗The invention discloses the bioactive nanoparticles composed of chitosan, poly-glutamic acid, and at least one bioactive agent characterized with a positive surface charge and enhanced permeability in oral drug delivery.
1. A pharmaceutical composition of nanoparticles for oral administration in a subject, said nanoparticles consisting of a positively charged chitosan, a negatively charged substrate, one bioactive agent, and optionally a zero-charge compound, wherein a shell portion of said nanoparticles is dominated by said positively charged chitosan.
2. The pharmaceutical composition of claim 1 , wherein said nanoparticles are formed via a simple and mild ionic-gelation method.
3. The pharmaceutical composition of claim 1 , wherein said one bioactive agent is epigallocatechin gallate.
4. The pharmaceutical composition of claim 1 , wherein said chitosan of the nanoparticles is N-trimethyl chitosan.
5. The pharmaceutical composition of claim 1 , wherein said chitosan of the nanoparticles is chitosan-EDTA or chitosan derivatives.
6. The pharmaceutical composition of claim 1 , wherein said nanoparticles have an average diameter from about 50 nm to about 500 nm.
7. The pharmaceutical composition of claim 1 , wherein said nanoparticles are encapsulated in a capsule.
8. The pharmaceutical composition of claim 7 , wherein said capsule is treated with an enteric coating.
9. The pharmaceutical composition of claim 7 , wherein said capsule further comprises at least one permeation enhancer.
10. The pharmaceutical composition 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, chitosan, and chitosan derivatives.
11. The pharmaceutical composition of claim 7 , wherein said capsule further comprises a solubilizer or other pharmacopoeial excipients.
12. The pharmaceutical composition of claim 7 , wherein said nanoparticles are freeze-dried prior to being loaded within said capsule.
13. The pharmaceutical composition of claim 7 , wherein said capsule further comprises a protease inhibitor.
14. The pharmaceutical composition of claim 1 , wherein said nanoparticles are mixed with trehalose and freeze-dried thereafter.
15. The pharmaceutical composition of claim 1 , wherein said nanoparticles are treated with an enteric coating.
16. The pharmaceutical composition of claim 1 , wherein said zero-charge compound is a permeation enhancer.
17. The pharmaceutical composition of claim 1 , wherein said negatively charged substrate is selected from the group consisting of γ-PGA, α-PGA, derivatives of PGA, and water soluble salts of PGA.
18. The pharmaceutical composition of claim 1 , wherein said nanoparticles are loaded in a tablet for said oral administration.
19. The pharmaceutical composition of claim 18 , wherein said tablet is treated with an enteric coating.
20. The pharmaceutical composition of claim 1 , wherein said chitosan has a molecular weight about 80 KDa or less.