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 of manufacturing an orally deliverable pharmaceutical composition, the method comprising steps of: (a) providing a drug carrier; (b) providing bioactive nanoparticles, wherein said nanoparticles consist of a positively charged chitosan, a negatively charged substrate, optionally a zero-charge compound, and at least one bioactive agent, wherein a shell portion of said nanoparticles is dominated by said positively charged chitosan; and (c) loading said bioactive nanoparticles in said drug carrier, thereby producing the orally deliverable pharmaceutical composition.
2. The method of claim 1 , wherein said bioactive nanoparticles have a mean particle size between about 50 and 400 nanometers.
3. The method of claim 1 , wherein the drug carrier is a capsule or tablet.
4. The method of claim 1 , wherein the drug carrier is a liquid carrier.
5. The method of claim 1 , further comprising a step of freeze-drying said bioactive nanoparticles prior to the loading step.
6. The method of claim 5 , wherein said bioactive nanoparticles are mixed with a coating compound prior to the freeze-drying step.
7. The method of claim 6 , wherein said coating compound is trehalose or mannitol.
8. The method of claim 1 , wherein said chitosan is N-trimethyl chitosan or a chitosan derivative.
9. The method of claim 1 , wherein said zero-charge compound is a transport enhancer.
10. The method of claim 9 , wherein said at least one transport enhancer is selected from the group consisting of bile salts, anionic surfactants, medium-chain fatty acids, and phosphate esters.
11. The method of claim 1 , wherein said pharmaceutical composition further comprises excipients during the loading step.
12. The method of claim 1 , wherein said nanoparticles are formed via a simple and mild ionic-gelation method.
13. The method of claim 1 , wherein said at least one bioactive agent is a protein or peptide.
14. The method of claim 1 , wherein said at least one bioactive agent is siRNA.
15. The method of claim 1 , wherein said nanoparticles are treated with alginate-calcium coating prior to the loading step.
16. The method of claim 1 , wherein said at least one bioactive agent is insulin or insulin analog.
17. The method of claim 1 , wherein said at least one bioactive agent is a hydrophilic molecule.
18. The method of claim 1 , wherein said at least one bioactive agent is erythropoietin hormone.
19. The method of claim 1 , wherein said at least one bioactive agent is heparin.
20. The method of claim 1 , wherein said at least one bioactive agent is small molecular weight heparin.