Gadolinium expressed lipid nanoparticles for magnetic resonance imaging

Patent metadata

Field	Value
Publication number	US-11207430-B2
Application number	US-201615369661-A
Country	US
Kind code	B2
Filing date	Dec 5, 2016
Priority date	Feb 13, 2009
Publication date	Dec 28, 2021
Grant date	Dec 28, 2021

Abstract

Lipid nanoparticles expressing metal ions and methods for using the compositions for magnetic resonance imaging.

First claim

The invention claimed is:

1. A nanoparticle, comprising:
(a) a phospholipid selected from distearoyl-phosphocholine (DSPC) or dipalmitoyl sphingomyelin (DPSP);
(b) |N-(carbonyl-methoxypolyethyleneglycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG-DSPE); and
(c) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-diethylenetriaminepenta-acetyl (DSPE-DTPA) with a chelated Gd 3+ ion, wherein the nanoparticle is not a liposome, and wherein the nanoparticle has a T1 relaxivity constant (r 1 ) of at least about 133 sec −1 mM −1 as determined by a magnetic resonance (MR) scanner;
wherein the mPEG-DSPE is present in the amount from about 5 to about 20 mole percent of the combined phospholipid, the mPEG-DSPE, and DSPE-DTPA, and
wherein the phospholipid:mPEG-DSPE:DSPE-DTPA ratio is from 8:1:0.9 to 8:2:1.

2. The nanoparticle of claim 1 , wherein the N-(carbony]l-methoxypolyethyleneglycol)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG-DSPE) is N-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG-2000-DSPE).

3. The nanoparticle of claim 1 , further comprising a targeting moiety.

4. The nanoparticle of claim 3 , wherein the targeting moiety is selected from the group consisting of a protein, a polypeptide, a peptide, an antibody or fragment thereof, a small molecule, a sugar or polysaccharide or derivative thereof, and a nucleic acid.

5. A composition, comprising a carrier and a plurality of the nanoparticles of claim 1 .

6. The nanoparticle of claim 1 , wherein the nanoparticle comprises 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and N-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-distearoyl-sn-glycero-3 phosphoethanolamine (mPEG-2000-DSPE).

7. The nanoparticle of claim 1 , wherein the nanoparticle does not have a solid core structure.

Assignees

• Univ Washington

Inventors

• Ho Rodney J Y
• Hoekman John D
• Maravilla Ken

Classifications

• A61K49/085 Primary

  conjugated systems · CPC title

• A61K51/0497

  conjugates with a carrier being an organic compounds · CPC title

• A61K51/1251

  micro- or nanospheres, micro- or nanobeads, micro- or nanocapsules · CPC title

• A61K51/1227

  Micelles, e.g. phospholipidic or polymeric micelles · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title