Nanoparticles for protein drug delivery

• US 7,282,194 B2
• Filed: 11/21/2005
• Issued: 10/16/2007
• Est. Priority Date: 10/05/2004
• Status: Expired due to Fees

• Current Assignee: Nanomega Medical Corporation
• Original Assignee: GP Medical, Inc., National Tsing Hua University
• Inventors: Sung, Hsing-Wen, Tu, Hosheng, Lin, Yu-Hsin, Liang, Hsiang-Fa
• Primary Examiner(s): Monshipouri; Maryam
• Application Number:
  US11/284,734
• Publication Number:
  US 20060147539A1
• Time in Patent Office: 694 Days
• Field of Search: 424/501, 424/1.69, 424/1.73
• US Class Current: 424/1.69
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/7008 Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/5146 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: Y10S 977/773 Nanoparticle, i.e. structure having three dimensions of 100 nm or less

Abstract

The invention discloses the nanoparticles composed of chitosan, poly-γ-glutamic acid, and at least one bioactive agent characterized with a positive surface charge and their enhanced permeability for paracellular drug delivery.

Claims

1. A pharmaceutical composition of nanoparticles characterized by enhancing intestinal paracellular transport, each nanoparticle comprising a first component of at least one bioactive agent, a second component of low molecular weight chitosan, and a third component that is negatively charged, wherein said second component dominates on a surface of said nanoparticle.

2. The pharmaceutical composition of claim 1, wherein said third component is γ

-PGA.

3. The pharmaceutical composition of claim 2, wherein the first component comprises insulin at a concentration range of 0.075 to 0.091 mg/ml, the second component at a concentration range of 0.67 to 0.83 mg/ml, and the third component at a concentration range of 0.150 to 0.184 mg/ml.

4. The pharmaceutical composition of claim 1, wherein said third component is alginate.

5. The pharmaceutical composition of claim 1, wherein the at least one bioactive agent is an antagonist for Alzheimer'"'"'s disease.

6. The pharmaceutical composition of claim 1, wherein the at least one bioactive agent is memantine hydrochloride.

7. The pharmaceutical composition of claim 1, wherein the at least one bioactive agent is insulin or insulin analog.

8. The pharmaceutical composition of claim 1, wherein the at least one bioactive agent is a peptide.

9. The pharmaceutical composition of claim 1, wherein said nanoparticles are further encapsulated in a gelcap.

10. The pharmaceutical composition of claim 1, wherein said second component is crosslinked.

11. The pharmaceutical composition of claim 10, wherein the second component is crosslinked at a degree of crosslinking less than 50%.

12. The pharmaceutical composition of claim 10, wherein the second component is crosslinked at a degree of crosslinking ranged between 1% and 20%.

13. The pharmaceutical composition of claim 10, wherein the second component is crosslinked with a crosslinking agent selected from a group consisting of genipin, its derivatives, analogs, stereoisomers and mixtures thereof.

14. The pharmaceutical composition of claim 10, wherein the second component is crosslinked with epoxy compounds.

15. The pharmaceutical composition of claim 1, wherein the low molecular weight chitosan has a molecular weight of 80 kDa or less.

16. The pharmaceutical composition of claim 1, wherein the low molecular weight chitosan is further grafted with a polymer having a chemical formula as:

17. The pharmaceutical composition of claim 1, wherein a surface of the nanoparticles is characterized with a positive surface charge.

18. The pharmaceutical composition of claim 1, wherein the at least one bioactive agent is heparin.