Particle delivery

Abstract

A needleless syringe capable of accelerating particles comprising a therapeutic agent across skin or mucosal tissue of a vertebrate subject is provided. The syringe comprises a body having a lumen with a diaphragm located adjacent to a terminus thereof. Particles comprising a therapeutic agent are delivered from an external surface of the diaphragm by means of the motive force provided by the impact of a gaseous shock upon the internal surface of the diaphragm. A method for transdermally delivering particles comprising a therapeutic agent from the needleless syringe is also provided.

We claim:  
     
         1 . A needleless syringe capable of accelerating particles comprising a therapeutic agent across skin or mucosal tissue of a vertebrate subject, said syringe comprising: 
 (a) a body having a lumen therein, wherein said lumen has an upstream terminus and a downstream terminus and the upstream terminus of the lumen is capable of interfacing with an energizing means; and    (b) a diaphragm arranged adjacent to the downstream terminus of the lumen, said diaphragm having an internal surface facing the lumen and an external surface, wherein said diaphragm is moveable between an initial position in which a concavity is provided on the external surface of the diaphragm, and a dynamic position in which the external surface of the diaphragm is substantially convex.    
     
     
         2 . The needleless syringe of  claim 1 , wherein the diaphragm is an eversible dome-shaped membrane comprised of a flexible polymeric material.  
     
     
         3 . The needleless syringe of  claim 2 , wherein the flexible polymeric material is a polyurethane or a silicone rubber.  
     
     
         4 . The needleless syringe of  claim 1 , wherein the diaphragm is a bistable membrane that is moveable between an initial inverted position and a dynamic everted position.  
     
     
         5 . The needleless syringe of  claim 1  further comprising a rupture chamber having a first opening adapted to interface with an energizing means, and a second opening which is in fluid communication with the upstream terminus of the lumen.  
     
     
         6 . The needleless syringe of  claim 5 , wherein the second opening of the rupture chamber is closed by a rupturable membrane.  
     
     
         7 . The needleless syringe of  claim 1 , wherein the upstream terminus of the lumen is interfaced with a source of pressurized gas.  
     
     
         8 . The needleless syringe of  claim 6 , wherein the first opening of the rupture chamber is interfaced with a source of pressurized gas.  
     
     
         9 . The needleless syringe of  claim 7 , wherein the source of pressurized gas comprises a gas canister containing a releasable volume of a driving gas.  
     
     
         10 . The needleless syringe of  claim 9  further comprising valve means capable of actuation to release a volume of the pressurized gas from the canister and thereby create a gaseous shock wave within the lumen.  
     
     
         11 . The needleless syringe of  claim 10 , wherein the valve means comprises a rupturable membrane arranged over the upstream terminus of the lumen.  
     
     
         12 . The needleless syringe of  claim 10 , wherein the valve means comprises a frangible covering arranged over an opening in the gas canister.  
     
     
         13 . The needleless syringe of  claim 8 , wherein the source of pressurized gas comprises a gas canister containing a releasable volume of a driving gas.  
     
     
         14 . The needleless syringe of  claim 13 , wherein the gas canister and the rupture chamber have substantially the same volume.  
     
     
         15 . The needleless syringe of  claim 1 , wherein the lumen further contains a volume of a gas which is lighter than air.  
     
     
         16 . The needleless syringe of  claim 9 , wherein the driving gas is comprised of helium.  
     
     
         17 . The needleless syringe of  claim 1  further comprising particles comprising a therapeutic agent housed within the concavity in the external surface of the diaphragm.  
     
     
         18 . The needleless syringe of  claim 17 , wherein the particles are disposed between the external surface of the diaphragm and a retractable shield.  
     
     
         19 . The needleless syringe of  claim 17 , wherein the particles are disposed between the external surface of the diaphragm and a penetratable membrane.  
     
     
         20 . The needleless syringe of  claim 17 , wherein the particles are retained on the external surface of the diaphragm by an adhesive agent.  
     
     
         21 . The needleless syringe of  claim 20 , wherein the adhesive agent is selected from the group consisting of trehalose and silicone oil.  
     
     
         22 . The needleless syringe of  claim 1 , wherein the body comprises an elongate tubular structure and the diaphragm is arranged over the downstream terminus of the lumen.  
     
     
         23 . The needleless syringe of  claim 1 , wherein the body comprises an elongate tubular structure and the diaphragm is arranged over an opening adjacent to the downstream terminus of the lumen, said opening facing in a direction substantially perpendicular to the major axis of the lumen.  
     
     
         24 . A dome-shaped diaphragm for use with a needleless syringe, said diaphragm having a concavity sealably containing particles comprising a therapeutic agent.  
     
     
         25 . A method for transdermally delivering particles comprising a therapeutic agent from a needleless syringe, said method comprising: 
 (a) providing a needleless syringe having an eversible diaphragm with a convex surface and a concave surface, wherein particles comprising the therapeutic agent are disposed on the concave surface of the diaphragm; and    (b) releasing a gaseous shock wave in a direction toward the convex surface of the diaphragm with sufficient force to impel said diaphragm to an everted position, thereby dislodging the particles from the diaphragm and accelerating them toward a target surface.    
     
     
         26 . The method of  claim 25 , wherein the particles are accelerated toward a target mucosal surface.  
     
     
         27 . The method of  claim 25 , wherein the particles are accelerated toward the target surface in a direction substantially collinear with the direction of travel of the gaseous shock wave.  
     
     
         28 . The method of  claim 25 , wherein the particles are accelerated toward the target surface in a direction transverse to the direction of travel of the gaseous shock wave.  
     
     
         29 . The method of  claim 25 , wherein the diaphragm is a dome-shaped membrane comprised of a flexible polymeric material.  
     
     
         30 . The method of  claim 25 , wherein the diaphragm is a bistable membrane that is moveable between an initial inverted position and a dynamic everted position.