Nanoparticles for protein drug delivery
View Patent ↗The invention discloses bioactive nanoparticles composed of chitosan, poly-glutamic acid, and diethylenetriaminepentaacetic acid for use in radionuclide decorporation during radiological emergency. The chitosan-based nanoparticles are characterized with a positive surface charge and enhanced permeability for oral drug delivery.
1. A method of enhancing radionuclide decorporation in a subject comprising administering bioactive nanoparticles to said subject, wherein said nanoparticles comprise a shell portion that is dominated by positively charged chitosan, a core portion that contains a negatively charged substrate, wherein said negatively charged substrate is at least partially neutralized with a portion of said positively charged chitosan and at least one radionuclide-chelating agent.
2. The method of claim 1 , wherein the chitosan has a molecular weight about 80 kDa or less.
3. The method of claim 1 , wherein said nanoparticles have a mean particle size between about 50 and 400 nanometers.
4. The method of claim 1 , wherein the chitosan is N-trimethyl chitosan.
5. The method of claim 1 , wherein said nanoparticles are formed via a simple and mild ionic-gelation process.
6. The method of claim 1 , wherein said nanoparticles are loaded in tablets or pills.
7. The method of claim 6 , wherein said tablets or pills are treated with an enteric polymer.
8. The method of claim 1 , wherein said nanoparticles are encapsulated in capsules.
9. The method of claim 8 , wherein said capsules further comprise at least a solubilizer or pharmacopoeial excipients.
10. The method of claim 8 , wherein said capsules are treated with an enteric polymer.
11. The method of claim 8 , wherein said capsules further comprise at least one permeation enhancer.
12. The method of claim 11 , wherein said permeation enhancer is a Ca 2+ chelator.
13. The method of claim 8 , wherein said capsules further comprise diethylene triamine pentaacetic acid (DTPA).
14. The method of claim 1 , wherein said nanoparticles are freeze-dried, thereby said nanoparticles being in a powder form.
15. The method of claim 1 , wherein said nanoparticles are mixed with trehalose and then freeze-dried, thereby said nanoparticles being in a powder form.
16. The method of claim 1 , wherein said nanoparticles further comprise zinc.
17. The method of claim 1 , wherein said at least one radionuclide-chelating agent is diethylene triamine pentaacetic acid (DTPA).
18. The method of claim 1 , wherein said negatively charged substrate is a derivative of PGA.
19. The method of claim 1 , wherein said nanoparticles further comprise at least one permeation enhancer.
20. The method of claim 19 , wherein said permeation enhancer is a Ca 2+ chelator.