Nanoparticles for protein drug delivery
View Patent ↗The invention discloses the nanoparticles composed of chitosan, poly-glutamic acid, and at least one antibiotics or equivalent bioactive agent characterized with a positive surface charge and their enhanced permeability in oral drug delivery.
1. A method of treating infection caused by microorganisms in an animal subject, the method comprising administering chitosan-shelled nanoparticles to said subject, wherein each of said chitosan-shelled nanoparticles consists of positively charged chitosan, an antibiotic or bacteriophage, and a negatively charged substrate, wherein said negatively charged substrate is at least partially reacted with a portion of said positively charged chitosan in an inner portion of said nanoparticle.
2. The method of claim 1 , wherein said antibiotic is vancomycin.
3. The method of claim 1 , wherein said antibiotic is a glycylcycline antibiotic.
4. The method of claim 1 , wherein said antibiotic is a lincosamide antibiotic.
5. The method of claim 1 , wherein the chitosan has a molecular weight about 80 kDa or less.
6. The method of claim 1 , wherein said negatively charged substrate is γ-PGA, α-PGA, derivatives of PGA, or salts of PGA.
7. The method of claim 1 , wherein said nanoparticles are administered to said subject via a delivery method selected from the group consisting of an oral route, intravenous route, subcutaneous injection route, intramuscular route, buccal route, intranasal route, and parenteral route.
8. The method of claim 1 , wherein the chitosan is N-trimethyl chitosan, EDTA-chitosan, or chitosan derivatives.
9. The method of claim 1 , wherein said nanoparticles further comprise a permeation enhancer.
10. The method of claim 9 , wherein said permeation enhancer is selected from the group consisting of Ca 2+ chelators, bile salts, anionic surfactants, medium-chain fatty acids, phosphate esters, and chitosan derivatives.
11. The method of claim 1 , wherein said nanoparticles are freeze-dried, thereby said nanoparticles being in a powder form.
12. The method of claim 11 , wherein said nanoparticles are encapsulated in capsules.
13. The method of claim 12 , wherein said capsules are treated with an enteric coating.
14. The method of claim 13 , wherein said capsules further comprise a permeation enhancer.
15. The method of claim 14 , wherein said permeation enhancer is selected from the group consisting of Ca 2+ chelators, bile salts, anionic surfactants, medium-chain fatty acids, phosphate esters, chitosan, and chitosan derivatives.
16. The method of claim 13 , wherein said capsules further comprise a solubilizer or pharmacopoeial excipients.
17. The method of claim 1 , wherein said nanoparticles are mixed with trehalose and then freeze-dried, thereby said nanoparticles being in a powder form.
18. The method of claim 1 , wherein a surface of said nanoparticles is dominated by the positively charged chitosan.
19. The method of claim 1 , wherein at least a portion of said nanoparticles is crosslinked.
20. The method of claim 1 , wherein said antibiotic is a beta-lactam antibiotic or antitumor antibiotic.