Radiation and nanoparticles for enhancement of drug delivery in solid tumors

• US 6,165,440 A
• Filed: 07/09/1998
• Issued: 12/26/2000
• Est. Priority Date: 07/09/1997
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Esenaliev, Rinat O.
• Primary Examiner(s): Elliott, George C.
• Assistant Examiner(s): EPPS -SMITH, JANET L
• Application Number:
  US09/112,491
• Time in Patent Office: 901 Days
• Field of Search: 435/6, 435/91.1, 514/44, 604/21, 604/15, 604/102, 536/24.5
• US Class Current: 424/1.11
• CPC Class Codes: A61K 38/19 Cytokines; Lymphokines; Interferons
• 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 41/0038 Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy radiotherapy per se A61N5/10
• CPC Class Codes: A61K 41/0047 Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
• CPC Class Codes: A61K 47/6927 the form being a solid microparticle having no hollow or gas-filled cores
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention discloses a method/system utilizing interaction of electromagnetic pulses or ultrasonic radiation with nano- and microparticles for enhancement of drug delivery in solid tumors. The particles can be attached to antibodies directed against antigens in tumor vasculature and selectively delivered to tumor blood vessel walls. Cavitation induced by ultrasonic waves or local heating of the particles by pulsed electromagnetic radiation results in perforation of tumor blood vessels, microconvection in the interstitium, and perforation of cancer cell membrane, and therefore, provides enhanced delivery of macromolecular therapeutic agents from blood into cancer cells with minimal thermal and mechanical damage to normal tissues.

Claims

1. A method of enhancing anti-cancer drug delivery in a solid tumor, comprising the steps of:

administering at least one anti-cancer drug to said tumor;

injecting nanoparticles or microparticles to said tumor intravenously; and

irradiating said tumor with radiation.

2. The method of claim 1, wherein said anti-cancer drug is selected from the group consisting of a monoclonal antibody, a cytokine, an antisense oligonucleotide, and a gene-targeting vector.

3. The method of claim 1, wherein said tumor is in an organ selected from the group consisting of breast, lung, brain, liver, skin, kidney, GI organ, prostate, bladder and gynecological organ.

4. The method of claim 1, wherein said nanoparticles or microparticles are long-circulating particles with or without antibody coating.

5. The method of claim 4, wherein said antibody is directed against tumor vasculature.

6. The method of claim 1, wherein said nanoparticle has a diameter from about 0.1 nm to about 7000 nm.

7. The method of claim 1, wherein said nanoparticle or microparticle is selected from the group consisting of a metal particle, a carbon particle, a graphite particle, a polymer particle, a liquid particle and a porous particle.

8. The method of claim 1, wherein said radiation is optical pulsed radiation generated from a laser or non-laser source.

9. The method of claim 8, wherein said optical radiation is delivered through skin surface or via optical fibers or endoscopes to said tumor.

10. The method of claim 8, wherein said optical radiation is in the spectral range from 0.2 μ

m to 2 μ

m.

11. The method of claim 1, wherein said radiation is utrasonic radiation generated from an ultrasonic transducer.

12. The method of claim 11, wherein said ultrasonic radiation is in the frequency range from 20 to 500 kHz.

13. The method of claim 11, wherein said ultrasonic radiation is delivered through skin surface to said tumor.

14. An anti-cancer drug delivery system, comprising:

a source of radiation;

an electronic system for monitoring of said radiation;

a means for delivery of said radiation to said tumor;

nanoparticles or microparticles absorbing said radiation;

an injection means for administration of said anti-cancer drug and said nanoparticles or microparticles in blood.

15. A method of treating a solid tumor, comprising the steps of:

injecting nano- or microparticles to said tumor intravenously; and

irradiating said tumor with radiation.