Microprojection arrays with enhanced skin penetrating properties and methods thereof

Abstract

An apparatus for delivering an active ingredient into the skin of an animal at a defined depth, the apparatus including: a microprojection array including a plurality of microprojections having a density of at least 2,000 projections per cm 2 ; and an applicator that drives the microprojection array towards the skin in use so that the microprojection array impacts on the skin with a mass-to-velocity ratio of between 0.0005 g/m/s and 0.1 g/m/s per cm 2 .

1 . An apparatus for delivering an active ingredient into the skin of an animal at a defined depth, the apparatus including:
 a) a microprojection array including a plurality of microproj ections having a density of at least 2,000 projections per cm 2 ; and,   b) an applicator that drives the microprojection array towards the skin in use so that the microprojection array impacts on the skin with a mass-to-velocity ratio of between 0.0005 g/m/s and 0.1 g/m/s per cm 2 .   
     
     
         2 . The apparatus of  claim 1 , wherein the microprojection array impacts on the skin with a mass-to-velocity ratio of at least one of:
 a) less than 0.05 g/m/s;   b) less than 0.005 g/m/s; and,   c) between 0.033 g/m/s and 0.0008 g/m/s.   
     
     
         3 . The apparatus of  claim 1 , wherein the microprojection array impacts the skin with a mass between at least one of:
 a) 0.001 g and 5g;   b) 0.005 g and 2 g; and,   c) 0.02 g and 0.5 g.   
     
     
         4 . The apparatus of  claim 1 , wherein the microprojection array impacts the skin at velocities between:
 a) 5 m/s and 50 m/s;   b) 10 m/s and 30 m/s; and,   c) 15 m/s and 25 m/s.   
     
     
         5 . The apparatus of  claim 1 , wherein the microprojection array has an area between at least one of:
 a) 16 mm 2  and 400 mm 2 ;   b) 36 mm 2  and 225 mm 2 ; and,   c) 64 mm 2  and 100 mm 2 .   
     
     
         6 . The apparatus of  claim 1 , wherein the microprojection array has a microprojection density between 5,000 and 20,000 projections per cm 2 . 
     
     
         7 . The apparatus of  claim 1 , wherein the microprojections are at least one of:
 a) solid;   b) non-porous; and,   c) non-hollow.   
     
     
         8 . The apparatus of  claim 1 , wherein the microprojections are at least one of:
 a) tapered;   b) substantially conical;   c) substantially flattened;   d) hexagonal; and,   e) octagonal.   
     
     
         9 . The apparatus of  claim 1 , wherein the microprojections have a length of at least one of:
 a) more than 100 μm;   b) more than 200 μm;   c) less than 1000 μm;   d) less than 5000 μm; and,   e) between 200 μm and 300 μm.   
     
     
         10 . The apparatus of  claim 1 , wherein the microprojections include:
 a) a base having a width of about 5 μm to about 50 μm; and,   b) a tip having a width of about 0.5 μm to about 2 μm.   
     
     
         11 . The apparatus of  claim 1 , wherein the applicator includes a driver that drives the microprojection array towards the skin and wherein the microprojection array is releasably mounted to the driver so that the microprojection array is released from the driver prior to the microprojections contacting the skin. 
     
     
         12 . The apparatus of  claim 11 , wherein the driver abuts against a stop to thereby release the microprojection array. 
     
     
         13 . The apparatus of  claim 12 , wherein the stop includes an annular shoulder. 
     
     
         14 . The apparatus of  claim 12 , wherein the applicator includes:
 a) a housing containing the driver; and,   b) a substantially tubular spacer that in use is positioned with an open end in contact with a surface of the skin to thereby space the housing from the skin, the stop being provided proximate the open end of the spacer.   
     
     
         15 . The apparatus of  claim 14 , wherein the driver is urged from a retracted to an extended position using a biasing mechanism, and wherein the biasing mechanism and engagement between the driver and housing define a driver velocity in use. 
     
     
         16 . The apparatus of  claim 15 , wherein the driver is a piston. 
     
     
         17 . The apparatus of  claim 15 , wherein the biasing mechanism includes at least one of:
 a) a spring; and,   b) a pneumatic actuator.   
     
     
         18 . The apparatus of  claim 15 , wherein the engagement is frictional engagement between a piston and piston chamber within the housing. 
     
     
         19 . The apparatus of  claim 1 , wherein the microprojection array impacts on the skin with a mass-to-velocity ratio sufficiently high to effect at least one of:
 a) fracture the skin;   b) concentrate mechanical stress in superficial layers of the skin;   c) invoke strain-rate dependent skin stiffening;   d) cause consistent penetration independent of variations in subcutaneous properties of the skin;   e) dissipate inertia so as to avoid mechanical stress on body parts underlying the skin; and,   f) cause a controlled amount of mechanical stress for immune-enhancing inflammation.   
     
     
         20 . The apparatus of  claim 1 , wherein at least tips of the microprojections are coated. 
     
     
         21 . The apparatus of  claim 1 , wherein the active ingredient is one or more vaccine antigens. 
     
     
         22 . A method of determining the design of a microprojection array and the velocity for delivering the microprojection array to a predetermined range of skin depth comprising calculating the microprojection array density, microprojection array area, microprojection array mass and microprojection velocity to mass ratio to deliver the microprojection array to the predetermined depth range.