Nanoparticles for delivery of bioactive agents
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 efficiency for gene delivery and bioactive agent delivery.
1. A method of gene delivery to a subject, comprising administering a nanoparticulate vector composition to said subject, wherein said composition comprises chitosan-shelled nanoparticles having a network formed by electrostatically complexing a positively charged compound and a negatively charged organic substrate, wherein DNA, RNA, or siRNA is loaded within said network.
2. The method according to claim 1 , wherein said DNA comprises plasmid DNA.
3. The method according to claim 1 , wherein said negatively charged substrate is poly-glutamic acid (PGA).
4. The method according to claim 3 , wherein said PGA is γ-PGA, α-PGA, derivatives of PGA, salts of PGA, or PGA-DTPA conjugates.
5. The method according to claim 1 , wherein said nanoparticles are formed via a simple and mild ionic-gelation method.
6. The method according to claim 1 , wherein said positively charged compound is chitosan.
7. The method according to claim 6 , wherein said chitosan has a molecular weight about 80 kDa or less.
8. The method according to claim 6 , wherein said chitosan is N-trimethyl chitosan, EDTA-chitosan, or chitosan derivatives.
9. The method according to claim 1 , wherein said nanoparticles have a mean particle size between about 50 and 400 nanometers.
10. The method according to claim 1 , wherein said nanoparticles comprise collapsed nanoparticles or disintegrated nanoparticles.
11. The method according to claim 1 , wherein at least a portion of said nanoparticles is crosslinked.
12. The method according to claim 1 , wherein the method comprises subcutaneous injection or oral administration.
13. The method according to claim 1 , wherein said nanoparticles further comprise at least one bioactive agent.
14. The method according to claim 13 , wherein said bioactive agent comprises anti-epileptic drugs.
15. The method according to claim 13 , wherein said bioactive agent is an antagonist for treating Alzheimer's disease or an antagonist for treating Parkinson's disease.
16. The method according to claim 13 , wherein said bioactive agent comprises anti-HIV drugs.
17. The method according to claim 13 , wherein said bioactive agent is selected from the group consisting of tumor necrosis factor blockers, interferons, retroviral vectors, anti-inflammatory drugs, meningitis antagonists, and anti-oxidant drugs.
18. The method according to claim 1 , wherein said nanoparticles are freeze-dried.
19. The method according to claim 1 , wherein said nanoparticles further comprise an absorption enhancer.
20. The method according to claim 19 , wherein said enhancer is selected from the group consisting of Ca 2+ chelators, ethylenediaminetetraacetic acid (EDTA), bile salts, anionic surfactants, medium-chain fatty acids, phosphate esters, chitosan, and chitosan derivatives.