Pharmaceutical composition of nanoparticles for protein drug delivery
View Patent ↗The invention discloses a pharmaceutical composition of bioactive nanoparticles composed of chitosan, poly-glutamic acid, and a bioactive agent for oral delivery. The chitosan-based nanoparticles are characterized with a positive surface charge and enhanced permeability for oral drug delivery.
1. A composition of nanoparticles for treatment of an inflammatory disease of an animal subject, the bioactive nanoparticles consisting of at least one anti-inflammatory agent, positively charged chitosan, optionally a zero-charge substance and a negatively charged substrate of polyglutamic acid (PGA), wherein said negatively charged substrate is neutralized with a portion of said positively charged chitosan in a core portion of said nanoparticles.
2. The composition of claim 1 , wherein said anti-inflammatory agent is a monoclonal antibody.
3. The composition of claim 1 , wherein said anti-inflammatory agent is selected from the group consisting of infliximab, adalimumab, gemtuzumab ozogamicin, and trastuzumab.
4. The composition of claim 1 , wherein said chitosan is N-trimethyl chitosan, EDTA-chitosan, low molecular weight chitosan, PEG-chitosan, mono-N-carboxymethyl chitosan, chitosan derivatives, or combinations thereof.
5. The composition of claim 1 , wherein said nanoparticles are formulated into a tablet or pill configuration.
6. The composition of claim 5 , wherein said tablet or pill is treated with an enteric coating polymer.
7. The composition of claim 1 , wherein said nanoparticles are encapsulated in a capsule.
8. The composition of claim 7 , wherein said capsule further comprises a pharmaceutically acceptable carrier, diluent, excipient, solubilizer, bubbling agent, or emulsifier.
9. The composition of claim 7 , wherein said capsule is treated with an enteric coating polymer.
10. The composition of claim 7 , wherein said capsule further comprises at least one permeation enhancer.
11. The composition of claim 10 , wherein said permeation enhancer is selected from the group consisting of Ca 2+ chelators, bile salts, surfactants, medium-chain fatty acids, phosphate esters, chitosan, and chitosan derivatives.
12. The composition of claim 1 , wherein said nanoparticles are freeze-dried, thereby said nanoparticles being in a powder form.
13. The composition of claim 1 , wherein said nanoparticles are mixed with trehalose and then freeze-dried, thereby said nanoparticles being in a powder form.
14. The composition of claim 1 , wherein said nanoparticles are treated with an enteric coating polymer.
15. The composition of claim 1 , wherein said PGA is selected from the group consisting of a PGA-complexone conjugate, γ-PGA, α-PGA, derivatives of PGA, salts of PGA, and combinations thereof.
16. The composition of claim 15 , wherein the PGA-complexone conjugate has chelated gadolinium.
17. The composition of claim 1 , wherein said zero-charge substance is a permeation enhancer.
18. The composition of claim 1 , wherein said inflammatory disease is an inflammatory bowel disease.
19. The composition of claim 1 , wherein the inflammatory disease is a Crohn's disease or ulcerative colitis.
20. The composition of claim 1 , wherein the anti-inflammatory agent is selected from the group consisting of nystatin, antifungal agent, itraconazole, fluconazole, mesalazine, prednisone, a TNF inhibitor, azathioprine (Imuran), methotrexate, and 6-mercaptopurine.