Pharmaceutical composition of nanoparticles
View Patent ↗The invention discloses a pharmaceutical composition of bioactive nanoparticles composed of chitosan, poly-glutamic acid, and a pegylated 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 pharmaceutical composition of nanoparticles, said nanoparticles consisting of a shell portion that is dominated by positively charged chitosan, a core portion that consists of said positively charged chitosan, one negatively charged substrate, at least one pegylated bioactive agent loaded within said nanoparticles, and optionally a zero-charge compound.
2. The pharmaceutical composition of claim 1 , wherein said nanoparticles have a mean particle size between about 50 and 400 nanometers.
3. The pharmaceutical composition of claim 1 , wherein said chitosan is N-trimethyl chitosan, EDTA-chitosan, low molecular weight chitosan, mono-N-carboxymethyl chitosan, chitosan derivatives, or combinations thereof.
4. The pharmaceutical composition of claim 1 , wherein said nanoparticles are formed via a simple and mild ionic-gelation process.
5. The pharmaceutical composition of claim 1 , wherein said nanoparticles are formulated into a tablet or pill configuration.
6. The pharmaceutical composition of claim 5 , wherein said tablet or pill is treated with an enteric coating.
7. The pharmaceutical composition of claim 1 , wherein said nanoparticles are encapsulated in a capsule.
8. The pharmaceutical composition of claim 7 , wherein said capsule further comprises a pharmaceutically acceptable carrier, diluent, or excipient.
9. The pharmaceutical composition of claim 7 , wherein said capsule further comprises at least a solubilizer, bubbling agent, or emulsifier.
10. The pharmaceutical composition of claim 7 , wherein said capsule is treated with an enteric coating.
11. The pharmaceutical composition of claim 7 , wherein said capsule further comprises at least one absorption enhancer.
12. The pharmaceutical composition of claim 11 , wherein said absorption enhancer is selected from the group consisting of Ca 2+ chelators, bile salts, surfactants, medium-chain fatty acids, phosphate esters, chitosan, and chitosan derivatives.
13. The pharmaceutical composition of claim 1 , wherein said nanoparticles are freeze-dried, thereby said nanoparticles being in a powder form.
14. The pharmaceutical composition of claim 1 , wherein said nanoparticles are mixed with trehalose and then freeze-dried, thereby said nanoparticles being in a powder form.
15. The pharmaceutical composition of claim 1 , wherein said nanoparticles are treated with an enteric coating.
16. The pharmaceutical composition of claim 1 , wherein said negatively charged substrate is PGA-complexone conjugate, γ-PGA, α-PGA, derivatives of PGA, or salts of PGA.
17. The pharmaceutical composition of claim 1 , wherein said zero-charge compound is an absorption enhancer.
18. The pharmaceutical composition of claim 1 , wherein said pegylated bioactive agent is protein or a peptide that is covalently attached with polyethylene glycol polymer chains.
19. The pharmaceutical composition of claim 1 , wherein said pegylated bioactive agent is an anti-diabetic drug that is covalently attached with polyethylene glycol polymer chains.
20. The pharmaceutical composition of claim 19 , wherein said pegylated anti-diabetic drug is selected from the group consisting of insulin, an insulin analog, GLP-1, a GLP-1 analog, an insulin sensitizer, an insulin secretagogue, an inhibitor of dipeptidyl peptidase 4, metformin, alpha-glucosidase inhibitors, amylin analog, sodium-glucose co-transporter type 2 (SGLT2) inhibitors, benfluorex, tolrestat, and combinations thereof.