# US 10,441,529 B2 · Cavitation-inducing polymeric nanoparticles > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,441,529 B2 - Document ID: US10441529B2 - Status: Granted - Kind: B2 - Application number: 15/037,664 - Filed: 2014-11-19 - Published: 2016-10-13 - Granted: 2019-10-15 - Earliest claimed: 2013-11-19 - Assignees: Oxsonics Limited - Applicants: Oxsonics Limited - Inventors: James Kwan; Rachel Myers; Constantin-Cassios Coussios; Apurva Shah - Web page: https://patentgrep.com/patent/US10441529B2 ## CPC - A61K 9/0009: {involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis} - A61B 8/0841: {for locating instruments} - A61K 9/5138: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 41/0028: {Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds} - A61K 49/223: {Microbubbles, hollow microspheres, free gas bubbles, gas microspheres} - A61M 37/00: Other apparatus for introducing media into the body (for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30); Percutany, i.e. introducing medicines into the body by diffusion through the skin (salt baths A61H33/04) - A61M 37/0092: {using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis} - A61P 35/00: Antineoplastic agents - C08F 257/02: on to polymers of styrene or alkyl-substituted styrenes - C08L 25/06: Polystyrene - C08L 51/003: {grafted on to macromolecular compounds obtained by reactions only involving unsaturated carbon-to-carbon bonds (C08L51/04, C08L51/06 take precedence)} - A61B 8/481: {involving the use of contrast agents, e.g. microbubbles introduced into the bloodstream} - C08L 2203/02: for biomedical use - 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) - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS - C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06) ## Abstract The invention disclosed herein relates to a nanoparticle comprising: a cup having a cavity, and a gas pocket present in the cavity, wherein the gas pocket is partially encapsulated by the cup. Typical uses of the nanocups include initiating inertial cavitation during simultaneous exposure to ultrasound, and/or as drug carriers to achieve targeted drug delivery in response to ultrasound excitation. ## Claims ### Claim 1 A pharmaceutical composition comprising a plurality of polymeric nanoparticles and a pharmaceutically acceptable carrier or diluent which is a liquid medium, wherein each polymeric nanoparticle comprises: a cup having a cavity, wherein at least a part of the cavity is substantially part-spherical with an opening of at least 50 nm, and a gas pocket present in the cavity, wherein the gas pocket is partially encapsulated by the cup, and wherein the polymeric nanoparticle comprises a single cup having a gas pocket present therein. ### Claim 2 (depends on 1) A pharmaceutical composition according to claim 1 wherein the cup is substantially part-spherical. ### Claim 3 (depends on 2) A pharmaceutical composition according to claim 2 wherein the cup is substantially hemi-spherical. ### Claim 4 (depends on 1) A pharmaceutical composition according to claim 1 wherein the cup has a substantially uniform wall thickness. ### Claim 5 (depends on 4) A pharmaceutical composition according to claim 4 wherein the cup has a wall thickness of 10 to 100 nm. ### Claim 6 (depends on 5) A pharmaceutical composition according to claim 5 wherein the cup has a wall thickness of 30 to 70 nm. ### Claim 7 (depends on 1) A pharmaceutical composition according to claim 1 wherein the opening of the cavity is from 50 to 900 nm. ### Claim 8 (depends on 7) A pharmaceutical composition according to claim 7 wherein the opening of the cavity is from 50 to 400 nm. ### Claim 9 (depends on 8) A pharmaceutical composition according to claim 8 wherein the polymeric nanoparticle is from 60 to 500 nm in size. ### Claim 10 (depends on 1) A pharmaceutical composition according to claim 1 wherein both the cup and the cavity are substantially part spherical, the cup has a substantially uniform wall thickness of from 10 to 100 nm and the opening of the cavity has a diameter of from 50 to 900 nm. ### Claim 11 (depends on 10) A pharmaceutical composition according to claim 10 wherein the opening of the cavity is from 50 to 400 nm in size. ### Claim 12 (depends on 1) A pharmaceutical composition according to claim 1 wherein the cup has a depth of greater than 50 nm. ### Claim 13 (depends on 1) A pharmaceutical composition according to claim 1, wherein the polymer is made up of two or more different monomer units, one monomer unit predominantly being present at the inner surface of the cup and another monomer unit predominantly being present at the exterior surface of the cup. ### Claim 14 (depends on 1) A pharmaceutical composition according to claim 1 wherein the polymer is a co-polymer of methyl methacrylate (MMA) and 2-hydroxyethyl methacrylate (HEMA). ### Claim 15 (depends on 14) A pharmaceutical composition according to claim 14 wherein the polymer is obtainable by using divinylbenzene as a crosslinking agent in a free-radical polymerization reaction. ### Claim 16 (depends on 1) A pharmaceutical composition according to claim 1 wherein the polymer is a crosslinked polymer. ### Claim 17 (depends on 1) A pharmaceutical composition according to claim 1 wherein the polymeric nanoparticle comprises one or more release agents. ### Claim 18 (depends on 17) A pharmaceutical composition according to claim 17 wherein a release agent is present within the cup, on an exterior surface of the cup and/or in the cavity of the cup. ### Claim 19 (depends on 18) A pharmaceutical composition according to claim 18 wherein the polymeric nanoparticle comprises a first release agent in the cavity of the cup, and a second release agent on an exterior surface of the cup. ### Claim 20 (depends on 17) A pharmaceutical composition according to claim 17 wherein one or more release agents is a drug. ### Claim 21 (depends on 1) A composition according to claim 1, wherein the composition comprises polymeric nanoparticles having a polydispersity index of no more than 0.2. ### Claim 22 A method of producing a polymeric nanoparticle comprising: a cup having a cavity, wherein at least a part of the cavity is substantially part-spherical with an opening of at least 50 nm, and a gas pocket present in the cavity, wherein the gas pocket is partially encapsulated by the cup, and wherein the polymeric nanoparticle comprises a single cup having a gas pocket present therein, which method comprises: providing a seed particle; partially coating the seed particle, by carrying out polymerization on the surface of the seed particle to provide a polymer coating, wherein the polymer induces swelling and deformation to provide a cup having the cavity; drying the cup; providing gas to the cup to produce a pocket of the gas within the cavity; and resuspending the polymeric nanoparticle in a liquid medium. ### Claim 23 (depends on 22) A method according to claim 22, wherein the steps of drying and providing gas to the cup are carried out by drying the cup in air. ### Claim 24 (depends on 22) A method according to claim 22, wherein the seed particle is coated by carrying out emulsion polymerization in the presence of the seed particle, the polymerization being carried out using one or more monomers and/or pre-polymers and optionally a cross-linking agent. ### Claim 25 (depends on 24) A method according to claim 24 wherein the cross-linking agent is divinylbenzene. ### Claim 26 (depends on 25) A method according to claim 25, wherein the polymerization is a free-radical polymerization. ### Claim 27 (depends on 22) A method according to claim 22, wherein the seed particle has a diameter of from 100 to 600 nm. ### Claim 28 (depends on 22) A method according to claim 22, wherein the polymeric nanoparticle comprises one or more release agents, and the method further comprises providing a release agent (a) as a coating on the seed particle; and/or (b) during polymerization; and/or (c) to the exterior surface of the cup. ### Claim 29 (depends on 28) A method according to claim 28, wherein two or more different release agents are provided. ### Claim 30 A method of treatment or diagnosis of a human or animal subject, wherein the method comprises administering to the subject a pharmaceutical composition comprising a plurality of polymeric nanoparticles, each polymeric nanoparticle comprising: a cup having a cavity, wherein at least a part of the cavity is substantially part-spherical with an opening of at least 50 nm, and a gas pocket present in the cavity, wherein the gas pocket is partially encapsulated by the cup, wherein the polymeric nanoparticle comprises a single cup having a gas pocket present therein, and wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or diluent which is a liquid medium; and exposing the subject to ultrasound. ### Claim 31 (depends on 30) The method of claim 30, wherein the ultrasound has a pressure amplitude of less than 5 MPa. ### Claim 32 (depends on 30) The method of claim 30, wherein the method is for the treatment or diagnosis of a tumor. ### Claim 33 (depends on 30) The method of claim 30, wherein the polymeric nanoparticle comprises one or more release agents, wherein the one or more release agents is a drug, and wherein the drug is released from the polymeric nanoparticle upon exposure to ultrasound. ### Claim 34 (depends on 30) The method of claim 30, wherein the polymeric nanoparticle comprises a first release agent in the cavity of the cup, and a second release agent on an exterior surface of the cup, and wherein the first and second release agents mix upon exposure of the polymeric nanoparticle to ultrasound.