Pharmaceutical composition of nanoparticles
View Patent ↗The invention discloses a pharmaceutical composition of the nanoparticles composed of chitosan, a negatively charged substrate, a transition metal ion, and at least one bioactive agent for drug delivery. The nanoparticles are characterized with a positive surface charge configured for promoting enhanced permeability for bioactive agent delivery.
1. A pharmaceutical composition of nanoparticles, the nanoparticles consisting of a shell portion that is dominated by positively charged chitosan and a core portion, wherein the core portion consists of the positively charged chitosan, a transition metal ion, one negatively charged substrate, at least one bioactive agent loaded within the nanoparticles, and optionally a zero-charge compound.
2. The pharmaceutical composition of claim 1 , wherein the negatively charged substrate is polyglutamic acid (PGA).
3. The pharmaceutical composition of claim 2 , wherein the PGA is selected from the group consisting of γ-PGA, α-PGA, PGA-complexone conjugate, derivatives of PGA, or salts of PGA.
4. The pharmaceutical composition of claim 3 , wherein the complexone in the PGA-complexone conjugate is selected from the group consisting of diethylene triamine pentaacetic acid (DTPA), ethylene diamine tetraacetic acid (EDTA), ethylene glycol tetraacetic acid (EGTA), N,N-bis(carboxymethyl)glycine, nitrilotriacetic acid (NTA), 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), poly(acrylic acid), methoxyacetic acid (MA), ethoxyacetic acid (EAA), propoxyacetic acid, butoxyacetic acid (BAA), and pentoxyacetic acid (PEAA).
5. The pharmaceutical composition of claim 1 , wherein the chitosan is N-trimethyl chitosan, EDTA-chitosan, low molecular weight chitosan, chitosan derivatives, or combinations thereof.
6. The pharmaceutical composition of claim 1 , wherein the transition metal ion enhances forming coordinate-covalent bonds between the chitosan and the bioactive agent leading to increased loading efficiency of the bioactive agent in the nanoparticles.
7. The pharmaceutical composition of claim 1 , wherein the zero-charge compound comprise a pharmaceutically acceptable carrier, diluent, or excipient.
8. The pharmaceutical composition of claim 1 , wherein said nanoparticles are orally administered to a patient.
9. The pharmaceutical composition of claim 1 , wherein the at least one bioactive agent is exendin-4.
10. The pharmaceutical composition of claim 1 , wherein the at least one bioactive agent is GLP-1 or GLP-1 analog.
11. The pharmaceutical composition of claim 1 , wherein the at least one bioactive agent is insulin or insulin analog.
12. The pharmaceutical composition of claim 1 , wherein the zero-charge compound is a permeation enhancer.
13. The pharmaceutical composition of claim 1 , wherein the nanoparticles are freeze-fried, thereby said nanoparticles being in a powder form.
14. The pharmaceutical composition of claim 1 , wherein the nanoparticles are mixed with trehalose and then freeze-fried, thereby said nanoparticles being in a powder form.
15. The pharmaceutical composition of claim 1 , wherein the nanoparticles are encapsulated in capsules.
16. The pharmaceutical composition of claim 15 , wherein the capsules are treated with an enteric coating.
17. The pharmaceutical composition of claim 15 , wherein the capsules further comprise a permeation enhancer.
18. The pharmaceutical composition of claim 1 , wherein the nanoparticles are administered to a patient via intravenous infusion, transdermal administration, or intranasal administration.
19. The pharmaceutical composition of claim 1 , wherein the nanoparticles are formed in tablets or pills configuration.