Transdermal delivery of encapsulated drugs

• US 5,814,599 A
• Filed: 08/04/1995
• Issued: 09/29/1998
• Est. Priority Date: 08/04/1995
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Langer, Robert S., Mitragotri, Samir S., Blankschtein, Daniel
• Primary Examiner(s): Tsang, Cecilia J.
• Assistant Examiner(s): HARLE, JENNIFER I
• Application Number:
  US08/511,583
• Time in Patent Office: 1,152 Days
• Field of Search: 604/20-23, 604/49, 604/304, 604/892.1, 604/290, 128/24, 128/632, 128/633, 128/760, 128/771, 424/450, 514/3
• US Class Current: 514/7.4
• CPC Class Codes: A61B 18/203 applying laser energy to the outside of the body
• CPC Class Codes: A61B 2017/00172 Pulse trains, bursts, intermittent continuous operation
• CPC Class Codes: A61B 2017/00765 Decreasing the barrier function of skin tissue by radiated energy, e.g. using ultrasound, using laser for skin perforation
• CPC Class Codes: A61B 2018/00452 Skin
• CPC Class Codes: A61B 2018/0047 Upper parts of the skin, e.g. skin peeling or treatment of wrinkles
• CPC Class Codes: A61B 2562/0295 Strip shaped analyte sensors for apparatus classified in A61B5/145 or A61B5/157 disposable multilayered or laminated electrodes G01N27/307; details of handling chemical test elements G01N33/4875
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/681 Wristwatch-type devices
• CPC Class Codes: A61K 41/0047 Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
• CPC Class Codes: A61K 49/22 Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
• 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 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 37/0092 using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428

Abstract

Applications of low-frequency (20 KHz) ultrasound enhances transdermal transport of high-molecular weight proteins. This method includes a simultaneous application of ultrasound and protein on the skin surface in order to deliver therapeutic doses of proteins across the skin. Examples demonstrate in vitro and in vivo administration of insulin (molecular weight 6,000 D), and in vitro administration of gamma interferon (molecular weight 17,000 D), and erythropoeitin (molecular weight 48,000 D).

Claims

1. A method for enhancing delivery of a drug across the skin comprising applying the drug encapsulated in a liposome or polymeric microparticle to the skin in a pharmaceutically acceptable carrier having an absorbance coefficient equivalent to water and applying ultrasound at a frequency of between 20 kHz and less than 10 MHz at an intensity not causing any irreversible skin damage for a period of time effective to deliver the drug encapsulated in the liposome or microparticle across the skin in a desired drug dosage.

2. The method of claim 1 wherein the drug is a peptide or protein.

3. The method of claim 1 wherein the encapsulating material is a liposome.

4. The method of claim 1 wherein the encapsulating material is a polymeric microparticle.

5. The method of claim 4 wherein the microparticle is coated with a lipophilic or hydrophilic material enhancing transdermal penetration.

6. The method of claim 5 wherein the material is a hydrophilic molecule coupled to a synthetic biodegradable polymer forming the microparticle.

7. The method of claim 1 wherein the frequency is between 20 and 45 kHz.

8. The method of claim 1 wherein the intensity is between zero and 1 W/cm².

9. The method of claim 5 wherein the intensity is between 12.5 mW/cm² and 225 mW/cm².