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. A method for controlled releasing a bioactive agent in blood circulation, comprising administering chitosan-shelled nanoparticles or collapsed chitosan-shelled nanoparticles into said blood circulation, wherein said nanoparticles or said collapsed nanoparticles consist of positively charged chitosan, a negatively charged substrate, and said bioactive agent, wherein a surface of said nanoparticles or said collapsed nanoparticles is dominated by the positively charged chitosan.
2. The method of claim 1 , wherein said nanoparticles or said collapsed nanoparticles are biodegradable.
3. The method of claim 1 , wherein said bioactive agent is heparin.
4. The method of claim 1 , wherein said negatively charged substrate is a glycosaminoglycan (GAG).
5. The method of claim 1 , wherein said negatively charged substrate is γ-PGA, α-PGA, a derivatives of PGA or a salts of PGA.
6. The method of claim 1 , wherein said nanoparticles are formed via a simple and mild ionic-gelation method.
7. The method of claim 1 , wherein said nanoparticles further comprise Zn 2+ , magnesium sulfate or sodium tripolyphosphate (TPP).
8. The method of claim 1 , wherein said nanoparticles have a mean, particle size between about 50 and 400 nanometers.
9. The method of claim 1 , wherein at least a portion of a shell portion of said nanoparticles or said collapsed nanoparticles is crosslinked.
10. The method of claim 1 , wherein said positively charged chitosan has a molecular weight about 80 kDa or less.
11. The method of claim 1 , wherein said chitosan is N-trimethyl chitosan or chitosan derivatives.
12. The method of claim 1 , wherein said bioactive agent comprises anti-inflammatory drugs.
13. The method of claim 1 , wherein said bioactive agent comprises anti-epileptic drugs.
14. The method of claim 1 , wherein said bioactive agent is Alzheimer's antagonist.
15. The method of claim 1 , wherein said bioactive agent comprises anti-HIV therapeutic drugs.
16. The method of claim 1 , wherein said nanoparticles are freeze-dried, thereby said nanoparticles being in a powder form.
17. The method of claim 1 , wherein said bioactive agent is interferon or interleukin.
18. The method of claim 1 , wherein said bioactive agent is a monoclonal antibody or siRNA.
19. The method of claim 1 , wherein said bioactive agent is a tumor necrosis factor.
20. The method of claim 1 , wherein said bioactive agent is protein or a peptide.