Nanoparticles for protein drug delivery
View Patent ↗The invention discloses particulate complexes composed of chitosan, poly-glutamic acid, and at least one bioactive agent, wherein equal moles of the positively charged chitosan and the negatively charged poly-glutamic acid substrate form an electrostatic network enabling improved loading the bioactive agent.
1. A composition of particulate complexes, said complexes consisting of a core portion of positively charged chitosan, a first negatively charged substrate, optionally a zero-charge compound and one bioactive agent, and an outer portion of a second negatively charged substrate wherein said particulate complexes have a mean complex size between about 50 and 400 nanometers.
2. The composition of claim 1 , wherein said chitosan is N-trimethyl chitosan, mono-N-carboxymethyl chitosan (MCC), N-palmitoyl chitosan (NPCS), EDTA-chitosan, low molecular weight chitosan, chitosan derivatives, or combinations thereof.
3. The composition of claim 1 , wherein said first negatively charged substrate is DNA, RNA, or a small interfering ribonucleic acid (siRNA).
4. The composition of claim 1 , wherein said core portion further comprises micelles.
5. The composition of claim 1 , wherein said second negatively charged substrate is selected from the group consisting of γ-PGA, α-PGA, PGA-complexone conjugate, water-soluble salts of PGA, metal salts of PGA, and glycosaminoglycans.
6. The composition of claim 1 , wherein said particulate complexes are formulated into a tablet or pill configuration.
7. The composition of claim 6 , wherein said tablet or pill is treated with an enteric polymer.
8. The composition of claim 1 , wherein said particulate complexes are encapsulated in a capsule.
9. The composition of claim 8 , wherein said capsule further comprises a pharmaceutically acceptable carrier, diluent, excipient, solubilizer, bubbling agent, or emulsifier.
10. The composition of claim 8 , wherein said capsule is treated with an enteric polymer.
11. The composition of claim 1 , wherein said particulate complexes are freeze-dried, thereby said nanoparticles being in a powder form.
12. The composition of claim 1 , wherein said particulate complexes are mixed with trehalose and then freeze-dried, thereby said nanoparticles being in a powder form.
13. The composition of claim 1 , wherein said particulate complexes are treated with an enteric polymer.
14. The composition of claim 1 , wherein said bioactive agent is selected from the group consisting of proteins, peptides, nucleosides, nucleotides, antiviral agents, antineoplastic agents, antibiotics, and anti-inflammatory drugs.
15. The composition of claim 1 , wherein said bioactive agent is an agent for treating Alzheimer's disease selected from the group consisting of memantine hydrochloride, donepezil hydrochloride, rivastigmine tartrate, galantamine hydrochloride, insulin, and tacrine hydrochloride.
16. The composition of claim 1 , wherein said bioactive agent is selected from the group consisting of anti-epileptic drugs, anti-HIV drugs, anti-oxidants, anti-neuromyelitis optica drugs, meningitis antagonist, and anti-multiple sclerosis drugs.
17. The composition of claim 1 , wherein said bioactive agent is an anti-diabetic compound.
18. The composition of claim 1 , wherein said one bioactive agent is heparin or low molecular weight heparin.
19. The composition of claim 1 , wherein said bioactive agent is selected from the group consisting of hormone, growth hormone, and human growth hormone.
20. The composition of claim 1 , wherein said bioactive agent is selected from the group consisting of calcitonin, cyclosporin, insulin, oxytocin, tyrosine, enkephalin, tyrotropin releasing hormone, follicle stimulating hormone, luteinizing hormone, vasopressin and vasopressin analogs, catalase, superoxide dismutase, interleukin-II, interferon, colony stimulating factor, tumor necrosis factor, anti tumor necrosis factor, erythropoietin, and melanocyte-stimulating hormone.