Process for preparing stealth nanoparticles

Patent metadata

Field	Value
Publication number	US-10967039-B2
Application number	US-201414894495-A
Country	US
Kind code	B2
Filing date	May 28, 2014
Priority date	May 28, 2013
Publication date	Apr 6, 2021
Grant date	Apr 6, 2021

Abstract

A process for the preparation of targeting nanoparticles of a poly(alkyl cyanoacrylate) homopolymer or copolymer, wherein said method comprises, in a single step, the anionic polymerisation of an oil-in-water miniemulsion as herein defined. The invention also relates to nanoparticles produced from said process and to their use in medicine.

First claim

The invention claimed is:

1. A process for the preparation of nanoparticles of a poly(alkyl cyanoacrylate) homopolymer or copolymer, wherein said method comprises, in a single step, the anionic polymerisation of an oil-in-water miniemulsion, wherein said miniemulsion comprises:
(i) at least one alkyl cyanoacrylate monomer;
(ii) at least two different polyalkylene glycols independently selected from the group consisting of polyethylene glycols (PEG), polypropylene glycols (PPG), and copolymers thereof; and
(iii) optionally one or more active agents,
wherein at least one of said polyalkylene glycols initiates the single step anionic polymerisation reaction.

2. The process for the preparation of nanoparticles of a poly(alkyl cyanoacrylate) homopolymer or copolymer in claim 1 , wherein at least one of said polyalkylene glycols is covalently attached to a targeting moiety.

3. The process as claimed in claim 1 , wherein said miniemulsion is prepared by the addition of said at least two polyalkylene glycols to an oil-in water miniemulsion comprising said at least one alkyl cyanoacrylate monomer and optionally said one or more active agents.

4. The process as claimed in claim 3 , wherein said nanoparticles are stealth nanoparticles.

5. The process as claimed in claim 3 , wherein said miniemulsion further comprises a radically polymerisable crosslinker selected from the group consisting of an anhydride and an acrylate.

6. The process as claimed in claim 3 , wherein said at least one alkyl cyanoacrylate monomer is selected from the group consisting of ethyl cyanoacrylate, butyl cyanoacrylate, isohexyl cyanoacrylate, octyl cyanoacrylate and derivatives and mixtures thereof.

7. The process as claimed in claim 3 , wherein at least one of the polyalkylene glycols is a polyethylene glycol, optionally further comprising a hydrophobic component.

8. The process of claim 7 , wherein at least one of the polyethylene glycols is a block copolymer of a polyethylene glycol block and polypropylene glycol block and wherein said copolymer comprises a hydroxy or amino end group attached to the polypropylene glycol block.

9. The process of claim 3 wherein the targeting moieties are selected from the group consisting of peptides, miniproteins, antibody fragments, affibody molecules, nanobodies and aptamers.

10. The process of claim 3 , wherein the targeting moieties are selected from the group consisting of peptides, antibody fragments, affibody molecules, nanobodies and aptamers.

11. The process of claim 3 wherein the active agent is a therapeutic agent selected from the group consisting of docetaxel, cabazitaxel, paclitaxel, 5-fluorouracil, sorafenib, AMG900, temsirolimus or everolimus.

12. The process of claim 3 wherein the active agent is selected from the group consisting of carboplatin, oxaliplatin, picoplatin, tetraplatin, satraplatin, cisplatin, platinum-DACH and ormaplatin.

13. The process of claim 3 wherein the active agent is an imaging agent selected from the group consisting of metals, metal salts, near infrared dyes, fluorescent dyes, PET/SPECT chelating agents, agents suitable for MRI or Raman spectroscopy and radiopharmaceutical s.

Assignees

• Sintef Tto As

Inventors

• Schmid Ruth
• Stenstad Per
• Morch Yrr
• Johnsen Heidi

Classifications

• A61K9/5146

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides · CPC title

• C08F283/06

  on to polyethers, polyoxymethylenes or polyacetals {(C08F283/004 takes precedence)} · CPC title

• A61K47/585

  Ion exchange resins, e.g. polystyrene sulfonic acid resin · CPC title

• A61K38/06 Primary

  Tripeptides · CPC title

• C08F222/324

  Alpha-cyano-acrylic acid butyl ester · CPC title