Transdermal delivery of high viscosity bioactive agents

Abstract

A device and method for delivery of a bioactive agent across a dermal barrier of a subject. The device including a microneedle with a channel and a plurality of nanostructures and microstructures located on the microneedle. The nanostructures and microstructures are arranged in a fractal-like pattern. A reservoir is in fluid communication with the channel and contains a composition having a viscosity of greater than about 5 centipoise and comprising a bioactive agent. The method includes penetrating a stratum corneum of the subject with the microneedle and transporting a composition through the microneedle at a rate of greater than about 0.4 mg/hr/cm2 based upon the surface area of the microneedle.

What is claimed is: 
     
         1 . A device for delivery of a bioactive agent across a dermal barrier, the device comprising:
 a microneedle and a plurality of nanostructures and microstructures located on the microneedle, the nanostructures and microstructures being arranged in a fractal-like pattern, wherein the microneedle further contains a channel; and   a reservoir that is in fluid communication with the channel of the microneedle and that contains a composition having a viscosity of greater than about 5 centipoise and comprising a bioactive agent.   
     
     
         2 . The device according to  claim 1 , wherein the composition includes the bioactive agent in a concentration of greater than about 5 mg/mL. 
     
     
         3 . The device according to  claim 2 , wherein the composition includes the bioactive agent in a concentration of from about 35 mg/mL to about 500 mg/mL. 
     
     
         4 . The device according to  claim 1 , wherein the bioactive agent has a molecular weight of greater than about 100 kDa. 
     
     
         5 . The device according to  claim 1 , wherein the bioactive agent is a protein therapeutic. 
     
     
         6 . The device according to  claim 1 , the composition further comprising one or more pharmaceutically acceptable excipients. 
     
     
         7 . The device according to  claim 6 , wherein the pharmaceutically acceptable excipient comprises a solvent, a penetration enhancer, a thickening agent, a wetting agent, a lubricant, or an emollient. 
     
     
         8 . The device according to  claim 1 , wherein at least a portion of the microstructures have a cross-sectional dimension of greater than about 500 nanometers and less than about 10 micrometers and the nanostructures have a cross-sectional dimension of less than about 500 nanometers and greater than about 5 nanometers. 
     
     
         9 . The device according to  claim 1 , wherein the fractal-like pattern has a fractal dimension of greater than about 1. 
     
     
         10 . The device according to  claim 1 , wherein at least a portion of the nanostructures have a height from about 10 nanometers to about 1 micrometer. 
     
     
         11 . The device according to  claim 1 , wherein at least a portion of the nanostructures have an aspect ratio of from about 0.2 to about 5. 
     
     
         12 . The device according to  claim 8 , wherein at least a portion of the nanostructures have a cross-sectional dimension of from about 100 to about 300 nanometers. 
     
     
         13 . The device according to  claim 8 , wherein the nanostructures have approximately the same cross-sectional dimension. 
     
     
         14 . The device according to  claim 8 , wherein a ratio of the cross-sectional dimension of two adjacent nanostructures to a center-to-center spacing between those two structures is between about 1:1 and about 1:4. 
     
     
         15 . The device according to  claim 8 , wherein at least a portion of the nanostructures have an equidistant spacing. 
     
     
         16 . A method for delivering a bioactive agent to a subject comprising:
 penetrating a stratum corneum of the subject with a microneedle, the microneedle comprising a plurality of nanostructures and microstructures located on the microneedle, the nanostructures and microstructures being arranged in a fractal-like pattern; and   transporting a composition through the microneedle at a rate of greater than about 0.4 mg/hr/cm2 based upon the surface area of the microneedle.   
     
     
         17 . The method according to  claim 16 , wherein the stratum corneum is a layer of a subject's skin, the skin including tight junctions between cells of the skin, the nanostructures rearranging tight junctions between the cells, thereby increasing porosity of the skin. 
     
     
         18 . The method according to  claim 17 , wherein the rearrangement of the tight junctions leads to an increase in the porosity of a second tissue type that is not in contact with the microneedle. 
     
     
         19 . The method according to  claim 18 , wherein the second tissue type is vascular tissue. 
     
     
         20 . The method according to  claim 16 , wherein the composition has a viscosity of greater than about 5 centipoise.