Effect of electric field and ultrasound for transdermal drug delivery

Abstract

Transdermal transport of molecules during sonophoresis (delivery or extraction) can be further enhanced by application of an electric field, for example, electroporation or iontophoresis. In a preferred embodiment the ultrasound is low frequency ultrasound which induces cavitation of the lipid layers of the stratum corneum (SC). This method provides higher drug transdermal fluxes, allows rapid control of transdermal fluxes, and allows drug delivery or analyte extraction at lower ultrasound intensities than when ultrasound is applied in the absence of an electric field.

We claim:  
     
         1 . A method for enhancing transdermal transport of compounds comprising administering to the skin an effective amount of ultrasound in combination with an electric field.  
     
     
         2 . The method of    claim 1    wherein the ultrasound is administered at a frequency of less than 2.5 MHz.  
     
     
         3 . The method of    claim 1    wherein the ultrasound is administered at a frequency of 1 MHz or less.  
     
     
         4 . The method of    claim 1    wherein the intensity of the ultrasound is less than 2.5 W/cm 2 .  
     
     
         5 . The method of    claim 1    wherein the intensity of the ultrasound is less than 1.5 W/cm 2 .  
     
     
         6 . The method of    claim 1    wherein the ultrasound is administered with agents enhancing solubility of the compounds to be transported in combination with agents enhancing the fluidity of lipid bilayers.  
     
     
         7 . The method of    claim 1    wherein the ultrasound is administered in combination with an electric force field selected from the group consisting of electroporation and iontophoresis.  
     
     
         8 . The method of    claim 1    wherein the compound to be transported is a drug the patient is in need of.  
     
     
         9 . The method of    claim 1    wherein the compound to be transported is an analyte to be measured.  
     
     
         10 . The method of    claim 1    wherein the electric field is pulsed.  
     
     
         11 . The method of    claim 1    wherein the ultrasound is pulsed.  
     
     
         12 . An apparatus for applying ultrasound and an electric field to skin in an amount effect to enhance transport of molecules through the skin without damaging the skin.