# US 7,611,690 B2 · Nanoparticles for protein drug delivery

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- Number: US 7,611,690 B2
- Document ID: US7611690B2
- Status: Granted
- Kind: B2
- Application number: 12/221,897
- Filed: 2008-08-07
- Published: 2009-01-08
- Granted: 2009-11-03
- Earliest claimed: 2005-01-04
- Assignees: GP Medical, Inc.; National Tsing Hua University
- Inventors: Hsing-Wen Sung; Yu-Hsin Lin; Hosheng Tu
- Web page: https://patentgrep.com/patent/US7611690B2

## CPC

- A61K 9/5161: {Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 9/5169: {Proteins, e.g. albumin, gelatin}
- A61K 38/28: Insulins
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

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

## Claims

### Claim 1

A pharmaceutical composition of nanoparticles for oral administration in a patient, said nanoparticles comprising a shell portion that is dominated by positively charged chitosan, a core portion that consists of one negatively charged substrate, wherein said substrate is PGA, wherein said negatively charged substrate is at least partially neutralized with a portion of said positively charged chitosan in the core portion, and at least one bioactive agent loaded within said nanoparticles, wherein said at least one bioactive agent comprises incretin mimetics or pramlintide.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein said incretin mimetics is exenatide.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein said PGA is selected from the group consisting of γ-PGA, α-PGA, water soluble salts of PGA, and metal salts of PGA.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein said nanoparticles are formed via a simple and mild ionic-gelation method.

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

The pharmaceutical composition of claim 1, wherein said nanoparticles are encapsulated in a capsule.

### Claim 7 (depends on 6)

The pharmaceutical composition of claim 6, wherein an exterior surface of said capsule is treated with an enteric coating.

### Claim 8 (depends on 6)

The pharmaceutical composition of claim 6, wherein an interior surface of said capsule is treated with a hydrophobic coating.

### Claim 9 (depends on 1)

The pharmaceutical composition of claim 1, wherein said nanoparticles have a mean particle size between about 50 and 400 nanometers.

### Claim 10 (depends on 1)

The pharmaceutical composition of claim 1, wherein at least a portion of said nanoparticles is crosslinked.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, wherein said chitosan has a molecular weight about 80 kDa or less.

### Claim 12 (depends on 1)

The pharmaceutical composition of claim 1, wherein said chitosan is trimethyl chitosan or chitosan derivatives.

### Claim 13 (depends on 1)

The pharmaceutical composition of claim 1, wherein said bioactive agent further comprises insulin or insulin analog.

### Claim 14 (depends on 1)

The pharmaceutical composition of claim 1, wherein said nanoparticles are freeze-dried.

### Claim 15 (depends on 1)

The pharmaceutical composition of claim 1, wherein said at least one bioactive agent further comprises sulfonylureas, metformin or thiazolinediones.

### Claim 16 (depends on 6)

The pharmaceutical composition of claim 6, wherein at least one permeation enhancer is co-encapsulated with said nanoparticles.

### Claim 17 (depends on 16)

The pharmaceutical composition of claim 16, wherein said at least one permeation enhancer is selected from the group consisting of Ca2+ chelators, bile salts, anionic surfactants, medium-chain fatty acids, phosphate esters, chitosan, and chitosan derivatives.