Nanoparticles for protein drug delivery
View Patent ↗The invention discloses the nanoparticles composed of chitosan, poly-glutamic acid, and at least one protein drug or bioactive agent characterized with a positive surface charge and their enhanced permeability for paracellular protein drug and bioactive agent delivery.
1. An orally deliverable pharmaceutical composition to an animal subject comprising: (a) a drug carrier; (b) bioactive nanoparticles loaded with said drug carrier, wherein said nanoparticles comprise a shell portion that is dominated by positively charged chitosan, a core portion that contains negatively charged substrate, wherein said negatively charged substrate is at least partially neutralized with a portion of said positively charged chitosan; and (c) at least one bioactive agent.
2. The pharmaceutical composition of claim 1 , in the form of a capsule.
3. The pharmaceutical composition of claim 2 , wherein said capsule is two-part hard gelatin capsule.
4. The pharmaceutical composition of claim 2 , wherein an exterior surface of said capsule is treated with enteric coating.
5. The pharmaceutical composition of claim 1 , wherein said bioactive agent is a hormone.
6. The pharmaceutical composition of claim 1 , wherein said bioactive agent is a growth hormone.
7. The pharmaceutical composition of claim 1 , wherein said negatively charged substrate is selected from the group consisting of γ-PGA, α-PGA, water soluble salts of PGA, and metal salts of PGA.
8. The pharmaceutical composition of claim 1 , wherein a substantial portion of a surface of said nanoparticles is characterized with a positive surface charge.
9. The pharmaceutical composition of claim 1 , wherein said negatively charged substrate comprises heparin.
10. The pharmaceutical composition of claim 1 , wherein said bioactive nanoparticles are freeze-dried prior to being loaded with said drug carrier.
11. The pharmaceutical composition of claim 1 , wherein said bioactive nanoparticles are mixed with trehalose and freeze-dried prior to being loaded with said drug carrier.
12. The pharmaceutical composition of claim 1 , wherein said bioactive agent is insulin or insulin analog.
13. The pharmaceutical composition of claim 1 , wherein said chitosan is N-trimethyl chitosan.
14. The pharmaceutical composition of claim 1 , wherein said nanoparticles further comprise at least one paracellular transport enhancer.
15. The pharmaceutical composition of claim 1 , wherein said bioactive agent is protein or peptide.
16. The pharmaceutical composition of claim 1 , wherein said bioactive agent is siRNA.
17. The pharmaceutical composition of claim 1 , wherein said nanoparticles further comprise magnesium sulfate or TPP.
18. The pharmaceutical composition of claim 1 , wherein the drug carrier is in the form of a tablet.
19. The pharmaceutical composition of claim 1 , wherein said bioactive agent is an erythropoietin hormone.
20. The pharmaceutical composition of claim 14 , wherein said paracellular transport enhancer is selected from the group consisting of Ca 2+ chelators, bile salts, anionic surfactants, medium-chain fatty acids, phosphate esters, and chitosan derivatives.