Formulation of acoustically activatable particles having low vaporization energy and methods for using same

Patent metadata

Field	Value
Publication number	US-11123302-B2
Application number	US-201615247840-A
Country	US
Kind code	B2
Filing date	Aug 25, 2016
Priority date	Oct 8, 2010
Publication date	Sep 21, 2021
Grant date	Sep 21, 2021

Abstract

Acoustically activatable particles having low vaporization energy are disclosed. A particle of material includes a first substance that includes at least one component that has a boiling point below 25° C. at atmospheric pressure. A second substance, different from the first substance, encapsulates the first substance to create the particle. The particle has a core consisting of a liquid and is an activatable phase change agent. The second substance includes a polymeric brush layer to prevent aggregation and coalescence.

First claim

What is claimed is:

1. A particle of material, comprising:
a first substance that consists of at least one perfluorocarbon and each perfluorocarbon of which the first substance consists has a boiling point below 25° C. at atmospheric pressure; and
a second substance, different from the first substance, that encapsulates the first substance in a shell to create the particle, wherein the particle has a core consisting of the first substance, which is a liquid at 25° C. and atmospheric pressure, wherein the particle is an activatable phase change agent and wherein the particle has a diameter of less than one micron.

2. The particle of material of claim 1 wherein the at least one perfluorocarbon of which the first substance consists comprises at least one of decafluorobutane (DFB) or octafluoropropane (OFP).

3. The particle of material of claim 1 wherein the second substance comprises an encapsulation material including at least one of a lipid, a protein, a polymer, a gel, a surfactant, a peptide, or a sugar.

4. The particle of material of claim 1 wherein the second substance comprises an encapsulation material including lung surfactants, amphiphiles, proteins, or their peptide components to form and stabilize bilayer and multilayer folds of the encapsulation material and to fully encapsulate the first substance.

5. The particle of material of claim 4 wherein the encapsulation material comprises amphiphiles, and the amphiphiles comprise at least one of: amphiphilic polymers and copolymers; amphiphilic peptides; amphiphilic dendrimers; or amphiphilic nucleic acids.

6. The particle of material of claim 1 wherein the at least one perfluorocarbon of which the first substance consists comprises a mixture of a plurality of different perfluorocarbons different from the second substance and each having a different activation energy, wherein an activation energy of the particle is adjustable based on the relative proportions of the plurality of different perfluorocarbons.

7. The particle of material of claim 6 wherein the first substance comprises a mixture of a first perfluorocarbon having a first activation energy and a second perfluorocarbon having a second activation energy in a one-to-one ratio and wherein the activation energy of the particle is approximately the average of the first and second activation energies.

8. The particle of material of claim 1 wherein the second substance includes a component that causes the second substance to attach to cells of a tissue within a target region.

9. The particle of material of claim 8 wherein the component of the second substance attaches to proteins expressed by the cells of the tissue within the target region.

10. The particle of material of claim 8 wherein the component of the second substance comprises tissue-specific targeting ligands.

11. The particle of material of claim 8 wherein the component of the second substance attaches to proteins expressed by a tumor, cancerous cells, or pre-cancerous cells.

12. The particle of material of claim 1 wherein the second substance contains a component that promotes intracellular uptake.

13. The particle of material of claim 1 comprising a therapeutic agent that enters into cells of a target region via sonoporation, vaporization, endocytosis, or contact-facilitated diffusion.

14. The particle of material of claim 1 comprising a therapeutic agent including at least one of: a drug to be delivered to a target region and genetic material to be inserted into cells of the target region.

15. The particle of material of claim 1 wherein the second substance includes a substance that causes the particle to be internalized within a cell.

16. The particle of material of claim 14 wherein the second substance includes a substance that causes the particle to target a specific component within a cell.

17. The particle of material of claim 1 wherein the second substance comprises or has at least one of:
a net negative or net positive charge to prevent aggregation and coalescence;
a chemical substance that causes plasm ids or genes to attach to the shell;
a gene or plasmid that is targeted for delivery to the target region; and
a cationic chemical.

Assignees

• Univ North Carolina Chapel Hill
• Univ Arizona
• Univ Colorado Regents

Inventors

• Dayton Paul A
• Sheeran Paul S
• Matsunaga Terry O
• Borden Mark A

Classifications

• A61K41/0028 Primary

  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 · CPC title

• A61K49/221

  characterised by the targeting agent or modifying agent linked to the acoustically-active agent · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• A61K49/226

  Solutes, emulsions, suspensions, dispersions, semi-solid forms, e.g. hydrogels · CPC title

• A61K49/0002

  General or multifunctional contrast agents, e.g. chelated agents · CPC title