# US 2016/0129132 A1 · Process for Preparing Stealth Nanoparticles > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2016/0129132 A1 - Document ID: US20160129132A1 - Status: Published application - Kind: A1 - Application number: 14/894,495 - Filed: 2014-05-28 - Published: 2016-05-12 - Earliest claimed: 2013-05-28 - Assignees: Sinvent AS - Applicants: Sintef Tto AS - Inventors: Ruth Schmid; Per Stenstad; Yrr Morch; Heidi Johnsen - Web page: https://patentgrep.com/patent/US20160129132A1 ## CPC - A61K 38/06: Tripeptides - A61K 9/5138: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides} - A61K 9/5192: {Processes} - A61K 47/585: {Ion exchange resins, e.g. polystyrene sulfonic acid resin} - A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol - A61K 47/6933: {the polymer being obtained by reactions only involving carbon to carbon, e.g. poly(meth)acrylate, polystyrene, polyvinylpyrrolidone or polyvinylalcohol} - A61K 47/6935: {the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol} - C08F 2/22: Emulsion polymerisation - C08F 283/06: on to polyethers, polyoxymethylenes or polyacetals {(C08F283/004 takes precedence)} - C08F 222/324: {Alpha-cyano-acrylic acid butyl ester} - 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) - C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS ## 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. ## Claims ### Claim at position 1 1-18. (canceled) ### Claim 19 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, wherein said miniemulsion comprises: (i) at least one alkyl cyanoacrylate monomer; (ii) at least two polyalkylene glycols selected from the group consisting of polyethylene glycols (PEG) and polypropylene glycols (PPG) or mixtures thereof, wherein at least one of said polyalkylene glycols is covalently attached to a targeting moiety; and (iii) optionally one or more active agents. ### Claim 20 A process for the preparation of targeting nanoparticles of a poly(alkyl cyanoacrylate) homopolymer or copolymer, wherein said method comprises adding at least two polyalkylene glycols selected from the group consisting of polyethylene glycols (PEG) and polypropylene glycols (PPG) or mixtures thereof, to an oil-in-water miniemulsion, wherein said miniemulsion comprises (i) at least one alkyl cyanoacrylate monomer; and (ii) optionally one or more active agents; and polymerising the resulting mixture by anionic polymerisation. ### Claim 21 (depends on 19) The process as claimed in claim 19, 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. ### Claim 22 (depends on 21) The process as claimed claim 21, wherein at least one of said polyalkylene glycols initiates the anionic polymerisation reaction. ### Claim 23 (depends on 22) The process as claimed in claim 22 wherein said nanoparticles are stealth nanoparticles. ### Claim 24 (depends on 21) The process as claimed in claim 21, wherein said miniemulsion further comprises a radically polymerisable crosslinker, preferably an anhydride or an acrylate. ### Claim 25 (depends on 21) The process as claimed in claim 21, wherein said at least one cyanoacrylate monomer is selected from the group consisting of ethyl cyanoacrylate, butyl cyanoacrylate, isohexyl cyanoacrylate, octyl cyanoacrylate and derivatives and mixtures thereof. ### Claim 26 (depends on 21) The process as claimed in claim 21, wherein at least one of the polyalkylene glycols is a polyethylene glycol, optionally further comprising a hydrophobic component, e.g. polypropylene oxide component. ### Claim 27 (depends on 26) The process of claim 26, wherein at least one of the polyethylene glycols is a block copolymer of a polyethylene glycol and polypropylene glycol and wherein preferably said copolymer comprises a hydroxy or amino end group attached to a polypropylene oxide block. ### Claim 28 (depends on 21) The process of claim 21 wherein the targeting moieties are selected from the group consisting of peptides, miniproteins, antibody fragments, affibody molecules, nanobodies and aptamers. ### Claim 29 (depends on 21) The process of claim 21, wherein the targeting moieties are selected from the group consisting of peptides, antibody fragments, affibody molecules, nanobodies and aptamers. ### Claim 30 (depends on 21) The process of claim 21 wherein the active agent is a therapeutic agent and is preferably docetaxel, cabazitaxel, paclitaxel, 5-fluorouracil, sorafenib, AMG900, temsirolimus or everolimus. ### Claim 31 (depends on 21) The process of any claim 21 wherein the active agent is carboplatin, oxaliplatin, picoplatin, tetraplatin, satraplatin, cisplatin, platinum-DACH or ormaplatin. ### Claim 32 (depends on 21) The process of claim 21 wherein the active agent is an imaging agent and is preferably 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 radiopharmaceuticals. ### Claim 33 A targeting nanoparticle of a poly(alkyl cyanoacrylate) homopolymer or copolymer manufactured by the anionic polymerisation of an oil-in-water miniemulsion, wherein said miniemulsion comprises (i) at least one alkyl cyanoacrylate monomer; (ii) at least two polyalkylene glycols selected from the group consisting of polyethylene glycols (PEG) and polypropylene glycols (PPG) or mixtures thereof, wherein at least one of said polyalkylene glycols is covalently attached to a targeting moiety; and (iii) optionally one or more active agents. ### Claim 34 (depends on 33) The targeting molecule of claim 33: 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; wherein at least one of said polyalkylene glycols initiates the anionic polymerisation reaction; wherein said nanoparticles are stealth nanoparticles; wherein said miniemulsion further comprises a radically polymerisable crosslinker, preferably an anhydride or an acrylate; wherein said at least one cyanoacrylate monomer is selected from the group consisting of ethyl cyanoacrylate, butyl cyanoacrylate, isohexyl cyanoacrylate, octyl cyanoacrylate and derivatives and mixtures thereof; wherein at least one of the polyalkylene glycols is a polyethylene glycol, optionally further comprising a hydrophobic component, e.g. polypropylene oxide component; wherein the targeting moieties are selected from the group consisting of peptides, miniproteins, antibody fragments, affibody molecules, nanobodies and aptamers; wherein the targeting moieties are selected from the group consisting of peptides, antibody fragments, affibody molecules, nanobodies and aptamers; wherein the active agent is a therapeutic agent and is preferably docetaxel, cabazitaxel, paclitaxel, 5-fluorouracil, sorafenib, AMG900, temsirolimus or everolimus; the active agent is carboplatin, oxaliplatin, picoplatin, tetraplatin, satraplatin, cisplatin, platinum-DACH or ormaplatin; the active agent is an imaging agent and is preferably 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 radiopharmaceuticals. ### Claim 35 (depends on 35) The targeting nanoparticle of claim 35 wherein said miniemulsion further comprises a radically polymerisable crosslinker, preferably an anhydride or an acrylate. ### Claim 36 (depends on 35) The targeting nanoparticles of claim 35 wherein at least one of the polyethylene glycols is a block copolymer of a polyethylene glycol and polypropylene glycol and wherein preferably said copolymer comprises a hydroxy or amino end group attached to a polypropylene oxide block. ### Claim 37 (depends on 34) A pharmaceutical composition comprising a targeting nanoparticle as defined in claim 34 and one or more pharmaceutically acceptable carriers, diluents or excipients. ### Claim 38 (depends on 34) A targeting nanoparticle as defined in claim 34 for use in drug delivery or molecular imaging.