Chelating amphiphilic polymers

Patent metadata

Field	Value
Publication number	US-9718929-B2
Application number	US-201514713256-A
Country	US
Kind code	B2
Filing date	May 15, 2015
Priority date	Sep 9, 2008
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

Abstract

Described are amphiphilic polymers that are provided with chelating moieties. The amphiphilic polymers are block copolymers comprising a hydrophilic block and a hydrophobic block, with the chelating moieties linked to the end-group of the hydrophilic block. The disclosed polymers are capable of self-assembly into structures such as micelles and polymersomes. With suitable metals present in the form of coordination complexes with the chelating moieties, the chelating amphiphilic polymers of the invention are suitable for use in various imaging techniques requiring metal labeling, such as MRI (T 1 /T 2 weighted contrast agents or CEST contrast agents) SPECT, PET or Spectral CT.

First claim

The invention claimed is:

1. A particle comprising:
a non-chelating amphiphilic polymer; and
a self-assembled structure, the self-assembled structure comprising a chelating amphiphilic polymer,
wherein the chelating amphiphilic polymer is capable of self-assembly,
wherein the chelating amphiphilic polymer comprises a hydrophilic block and a hydrophobic block,
wherein the hydrophilic block is provided with a chelating moiety,
wherein the chelating moiety is selected from the group consisting of DOTA, DTPA, HYNIC, and desferoxamine as an end-group wherein the hydrophilic block is a poly (ethylene oxide) block, preferably having a weight-average molecular weight of from 500 to 10,000, wherein the hydrophobic block has a Tg of below 70° C., wherein the hydrophobic block is selected from the group consisting of poly (butadiene), poly (isoprene), and poly (ethylethylene).

2. The particle according to claim 1 , wherein the non-chelating amphiphilic polymer comprises a poly (oxy ethylene) chain as a hydrophilic block, wherein the chain is longer than the hydophilic block of the chelating amphiphilic polymer.

3. The particle according to claim 1 , further comprising a drug.

4. A CEST MRI contrast agent comprising a particle in accordance with claim 1 , wherein the particle is a polymersome,
wherein the polymersome has a wall formed by a bilayer of one or more amphiphilic polymers,
wherein the bilayer comprises a chelating amphiphilic polymer,
wherein the wall encloses a cavity,
wherein the cavity comprises a pool of proton analytes,
wherein the proton analytes are capable of diffusion through the wall, wherein chelating moieties of the chelating amphiphilic polymers extending into the direction of the cavity comprise a chelated paramagnetic material.

5. The CEST MRI contrast agent according to claim 4 , wherein the CEST MRI contract agent has a non-spherical shape.

6. A SPECT or PET contrast agent comprising a particle in accordance with claim 1 ,
Wherein the particle is a polymer-stabilized oil-in-water emulsion,
Wherein chelating moieties of the chelating amphiphilic polymer are provided with a chelated radionuclide suitable for SPECT or PET.

7. A spectral CT contrast agent comprising a particle in accordance with claim 1 , wherein chelating moieties of the chelating amphiphilic polymer are provided with a high-Z material.

8. A method of making a particle, wherein the particle comprises a non-chelating amphiphilic polymer and a self-assembled structure, the self-assembled structure comprising a chelating amphiphilic polymer, wherein the chelating amphiphilic polymer is capable of self-assembly,
wherein the chelating amphiphilic polymer comprises a hydrophilic block and a hydrophobic block,
wherein the hydrophilic block is provided with a chelating moiety, wherein the chelating moiety is selected from the group consisting of DOTA, DTPA, HYNIC, and desferoxamine as an end-group,
wherein one or more of the chelating moieties comprises a metal ion in the form of a coordination complex,
wherein the metal ions are chelated at the inside, wherein a chelating amphiphilic polymer is subject to an aqueous environment so as to form a bilayer enclosing a cavity, wherein the chelating moieties are subjected to the formation of coordination complexes with metal ions prior to the formation of the bilayer, the method comprising:
creating the amphiphilic polymer; and
after creating the amphiphilic polymer coupling the chelating moiety to the hydrophilic block,
wherein the hydrophilic block is a poly (ethylene oxide) block, preferably having a weight-average molecular weight of from 500 to 10,000,
wherein the hydrophobic block has a Tg of below 70° C.,
wherein, the hydrophobic block is selected from the group consisting of poly (butadiene), poly (isoprene), and poly (ethylethylene).

Assignees

• Koninklijke Philips Nv

Inventors

• Gruell Holger
• De Vries Anke
• Langereis Sander
• Lub Johan
• Aussems-Custers Erica Maria Gerarda

Classifications

• A61K9/1075 Primary

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title

• A61K9/1273

  Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances · CPC title

• A61K51/1251

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

• C08G81/025 Primary

  containing polyether sequences · CPC title

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title