Nanoparticles for protein drug delivery
View Patent ↗The invention discloses the nanoparticles composed of chitosan, poly-glutamic acid, and at least one DNA/RNA or bioactive agent characterized with a positive surface charge and their enhanced permeability for gene delivery and bioactive agent delivery.
1. A nanoparticulate vector composition for gene delivery comprising chitosan-based nanoparticles or collapsed chitosan-based nanoparticles that is loaded with DNA or RNA, wherein said nanoparticles or said collapsed nanoparticles comprise a shell portion and an inner portion, wherein a surface of the shell portion is dominated by positively charged chitosan, and wherein the inner portion consists of a negatively charged substrate, the positively charged chitosan, and optionally a zero-charge substance.
2. The nanoparticulate vector composition of claim 1 , wherein said DNA comprises plasmid DNA.
3. The nanoparticulate vector composition of claim 1 , wherein said negatively charged substrate is poly-glutamic acid (PGA).
4. The nanoparticulate vector composition of claim 3 , wherein said PGA is γ-PGA, α-PGA, derivatives of PGA, or salts of PGA.
5. The nanoparticulate vector composition of claim 1 , wherein said nanoparticles are formed via a simple and mild ionic-gelation method.
6. The nanoparticulate vector composition of claim 1 , wherein said nanoparticles have a mean particle size between about 50 and 400 nanometers.
7. The nanoparticulate vector composition of claim 1 , wherein said nanoparticles are treated with an enteric coating.
8. The nanoparticulate vector composition of claim 1 , wherein at least a portion of said nanoparticles or collapsed nanoparticles is crosslinked.
9. The nanoparticulate vector composition of claim 1 , wherein said chitosan has a molecular weight about 80 kDa or less.
10. The nanoparticulate vector composition of claim 1 , wherein said chitosan is N-trimethyl chitosan, N-Palmitoyl chitosan, EDTA-chitosan, or chitosan derivatives.
11. The nanoparticulate vector composition of claim 1 , wherein said zero-charge substance is a bioactive agent.
12. The nanoparticulate vector composition of claim 11 , wherein said bioactive agent comprises anti-epileptic drugs.
13. The nanoparticulate vector composition of claim 11 , wherein said bioactive agent is Alzheimer's antagonist.
14. The nanoparticulate vector composition of claim 11 , wherein said bioactive agent comprises anti-HIV drugs.
15. The nanoparticulate vector composition of claim 11 , wherein said bioactive agent is selected from the group consisting of tumor necrosis factor blockers, interferons, retroviral vectors, anti-inflammatory drugs, meningitis antagonist, and anti-oxidant drugs.
16. The nanoparticulate vector composition of claim 11 , wherein said nanoparticles are freeze-dried.
17. The nanoparticulate vector composition of claim 16 , wherein said nanoparticles are treated with an enteric coating.
18. The nanoparticulate vector composition of claim 1 , wherein said RNA comprises a small interfering ribonucleic acid (siRNA).
19. The nanoparticulate vector composition of claim 1 , wherein said zero-charge substance is a permeation enhancer.
20. The nanoparticulate vector composition of claim 11 , wherein said bioactive agent is an anti-multiple sclerosis drug.