METHOD OF CONTROLLING A RELEASE OF A MATERIAL CARRIED BY ULTRASOUND SENSITIVE PARTICLES

• US 20100106078A1
• Filed: 03/03/2008
• Published: 04/29/2010
• Est. Priority Date: 03/09/2007
• Status: Active Grant

• Current Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Original Assignee: Koninklijke Philips Electronics N.V. (Koninklijke Philips N.V.)
• Inventors: Chin, Chien T., Dimitrova, Nevenka, Hall, Christopher S.
• Granted Patent: US 8,357,112 B2
• Time in Patent Office: Days
• US Class Current: 604/22
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: 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
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis

Abstract

This invention relates to a method and an apparatus of controlling a release of a material carried by ultrasound sensitive particles, the release being caused by irradiating the ultrasound sensitive particles with an ultrasonic pulse having acoustic properties selected so as to interact with the ultrasound sensitive particles and thus causing the release of the material. The ultrasound sensitive particles comprise sub-groups of ultrasound sensitive particles, the ultrasound sensitive particles within the same sub-group having their respective acoustic property causing each respective sub-group to interact independently with the sound wave.

Claims

1. A method of controlling a release of a material carried by ultrasound sensitive particles (116-118), the release being caused by irradiating the ultrasound sensitive particles (116-118) with an ultrasonic pulse (108) having acoustic properties selected so as to interact with the ultrasound sensitive particles (116-118) and thus causing the release of the material, wherein the ultrasound sensitive particles (116-118) comprise sub-groups (110-112) of ultrasound sensitive particles, the ultrasound sensitive particles within the same sub-group (110-112) having their respective acoustic property causing each respective sub-group to interact independently with the ultrasonic pulse (108).

2. A method according to claim 1, wherein the ultrasound sensitive particles (116-118) within the same sub-group (110-112) of ultrasound sensitive particles carry the same type of material.

3. A method according to claim 1, wherein the sub-groups (110-112) of ultrasound sensitive particles (116-118) comprise microbubbles containing the type of material therein.

4. A method according to claim 1, wherein the sub-groups (110-112) of ultrasound sensitive particles comprise microbubbles having a shell structure containing the type of material therein.

5. A method according to claim 4, wherein the shell structure within the same sub-group has similar physical property, the property being characteristic for the respective acoustic property.

6. A method according to claim 5, wherein the physical property is selected from:

the shell thickness,

the shell size,

the diameter of the shell,

geometrical shape of the shell,

over or under filling of the gas in the bubbles,

the quantity of therapeutic or inert material relative to the number of bubbles,

chemical composition of the shell,

the number density of particles, and

a combination thereof.

7. A method according to claim 1, wherein the sub-groups (110-112) of ultrasound sensitive particles are selected from:

microbubbles having a shell structure containing said type of material therein,

microbubbles containing said type of material therein

microbubbles in a solution containing the type of material therein

nanoparticles,

liposomes,

heat shock proteins, and

a combination thereof.

8. A method according to claim 1, wherein the material carried by ultrasound sensitive particles (116-118) is a biological material and is selected from:

pharmaceutical material,

polysaccharides,

lipids,

fatty acids,

steroids,

proteins,

enzymes,

deoxyribonucleic acid (DNA),

ribonucleic acid (RNA),

small interfering ribonucleic acid (siRNA),

inorganic artificial constructs,

nanoparticles

nanomachines,

chemicals intended to alter the composition or geometry of existing sub-groups of particles,

biochemical particles, and

a combination thereof.

9. A method according to claim 1, wherein the respective acoustic property of the ultrasound sensitive particles (116-118) within the same sub-group is a common resonance frequency or resonance frequency range.

10. A method according to claim 1, wherein the acoustic properties of the ultrasonic pulse (108) are selected from:

a frequency corresponding to the resonance frequency of the one or more of the sub-groups,

the pressure amplitude of the ultrasonic pulse,

the duration of the ultrasonic pulse,

an arbitrary waveform, and

a combination thereof.

11. A method according to claim 1, wherein the release of the material is carried out locally in or nearby a target tissue or cell (120) by releasing the material from at least one of the sub-groups (110-112) of the ultrasound sensitive particles.

12. A method according to claim 1, wherein the method is performed in-vivo or in cell culture, the method further comprising:

a. receiving at least one command (807) indicating at least one spatial delivery zone, each command indicating at least one type of material to be released at specific ratios,

b. imaging the spatial distribution (809) of the ultrasound sensitive particles, the imaging resulting in data indicting the spatial distribution of the ultrasound sensitive particles, and in response to the spatial data

c. irradiating the ultrasound sensitive particles (813) in the at least one delivery zone with an ultrasonic pulse, the property of the ultrasonic pulse being controlled such that the release of the material in the at least one delivery zone is in accordance to the at least one received command,

d. repeating steps b)-c) for each subsequent command until the received commands have been completed.

13. A method according to claim 12, wherein the commands further include information about the amount of material to be delivered at a given delivery zone or the mix of material to be delivered at a given delivery zone or the material to be released in order to modify the acoustic properties of the remaining ultrasound sensitive particles (116-118).

14. An apparatus (101) for controlling a release of a material carried by ultrasound sensitive particles (116-118), comprising:

a control unit (102) adapted to release a control signal,

an ultrasound transducer (103) adapted to be coupled to the control unit (102) for irradiating, in response to the control signal from the control unit (102), the ultrasound sensitive particles (116-118) with an ultrasonic pulse (108) having acoustic properties selected so as to interact with the ultrasound sensitive particles and thus causing the release of the material,

wherein the ultrasound sensitive particles comprise sub-groups (110-112) of ultrasound sensitive particles (116-118) each of the sub-groups having their respective acoustic property, the ultrasound transducer (103) being adapted to irradiate the ultrasound sensitive particles with ultrasonic pulse (108) having the acoustic properties of the sub-groups.

15. An apparatus according to claim 14, further comprising input means (104) for receiving instructions indicating at least one spatial delivery zone and the type of material to be released at the at least one spatial delivery zone.

16. An apparatus according to claim 15, further comprising:

an imaging means (105) adapted to be coupled to the control unit (102) for—

imaging the spatial distribution of the ultrasound sensitive particles (116-118), the imaging resulting in data indicting the spatial distribution of the ultrasound sensitive particles, wherein in response to the spatial data the control unit (102) instructs the ultrasound transducer (103) to irradiate the ultrasound sensitive particles (116-118) localized nearby the at least one spatial delivery zone (120) with the ultrasonic pulse (108), the acoustic property of the ultrasonic pulse being controlled such that the release of the material at the at least one spatial delivery zone is in accordance to the received instructions.

17. Ultrasound sensitive particles (116-118) comprising sub-groups (110-112) of ultrasound sensitive particles carrying material, the ultrasound sensitive particles within the same sub-group having their respective acoustic property.

18. Ultrasound sensitive particles according to claim 17, wherein the diameter of the ultrasound sensitive particles is less than 100 nm, such as less than 50 nm, such as less than 25 nm, such as less than 10 nm, such as less than 5 nm.

19. Ultrasound sensitive particles according to claim 17, wherein the particles within the same group carry the same type of material.

20. A use of ultrasound sensitive particles as claimed in claim 17 for delivering the material into cells or tissues.