Apparatus for electrically mediated delivery of therapeutic agents

Abstract

Apparatus for the delivery of an electrical field which facilitates the intracellular delivery of a therapeutic agent to a predetermined site within the tissue of a patient. The apparatus will comprise a plurality of penetrating electrodes arranged in a predetermined spatial relationship, each electrode with a cross sectional area contributing to the total cross sectional area of all electrodes, and structural means incorporating an inanimate source of energy operatively connected to the plurality of electrodes for deploying the electrodes, wherein the source of energy is sufficient to impart a force of at least 1000 pounds per square inch (0.7 kilogram per square millimeter) of total cross sectional area of all electrodes at the initiation of the deployment of the electrodes. The apparatus will also comprise means for generating an electrical field which facilitates the intracellular delivery of a therapeutic agent, which means is operatively connected to said electrodes at least in their deployed state.

1 . An apparatus for delivery of an electrical field which facilitates intracellular delivery of a therapeutic agent to a predetermined site within a tissue of a patient comprising:
 (a) a fluid reservoir for containing the therapeutic agent, wherein the fluid reservoir is operatively connected to at least one injection orifice;   (b) an actuator configured to transmit the therapeutic agent through the orifice to the predetermined site within the tissue of the patient;   (c) a plurality of penetrating electrodes arranged in a predetermined spatial relationship, each electrode with a cross sectional area contributing to a total cross-sectional area of all electrodes;   (d) an inanimate source of energy operatively connected to the actuation means, wherein the source of energy is configured to apply a force of at least 0.25 pounds (1.1 Newtons) through the fluid reservoir to the therapeutic agent; and   (e) an electrical field generator which facilitates the intracellular delivery of the therapeutic agent, wherein the electric field generator is operatively connected to the electrodes at least in deployed state.   
     
     
         2 . The apparatus of  claim 1 , further comprising an applicator housing the inanimate source of energy operatively connected to the plurality of electrodes for deploying the electrodes in a deployed state, and wherein the source of energy is sufficient to impart a force of at least 1000 pounds per square inch (0.7 kg/square millimeter) of the total cross sectional area of all electrodes at initiation of deployment of the electrodes. 
     
     
         3 . The apparatus of  claim 1 , further comprising a subassembly that can be separated from the source of energy, wherein the subassembly comprises a depth adjustor at a distal tip of the subassembly, wherein the depth adjustor can be adjusted axially relative to the distal tip such that moving the depth adjustor axially modifies a depth of penetration by the electrodes at the deployment. 
     
     
         4 . The apparatus of  claim 2 , wherein the source of energy to deploy the electrodes comprises a spring or a compressed gas. 
     
     
         5 . The apparatus of  claim 2 , wherein the source of energy to deploy the electrodes comprises a compressed gas. 
     
     
         6 . The apparatus of  claim 2 , wherein the source of energy to deploy the electrodes comprises a linear motor. 
     
     
         7 . The apparatus of  claim 1 , wherein the fluid reservoir comprises dual chambers. 
     
     
         8 . The apparatus of  claim 7 , wherein the dual chambers comprise a first chamber containing a lyophilized agent and a second chamber containing a diluent. 
     
     
         9 . The apparatus of  claim 1 , wherein the apparatus comprises a needle forming the injection orifice and a syringe forming the reservoir, and wherein the syringe is pre-filled with the therapeutic agent. 
     
     
         10 . The apparatus of  claim 3 , wherein the subassembly houses the electrodes, the reservoir, and the injection orifice. 
     
     
         11 . The apparatus of  claim 3 , wherein the subassembly incorporates operative connections for the electrodes, the reservoir, and the injection orifice, wherein the subassembly is configured to allow disposition of the plurality of electrodes and the injection orifice within the tissue of the patient according to a predetermined spatial relationship. 
     
     
         12 . The apparatus of  claim 3 , wherein the subassembly comprises a needle and a syringe. 
     
     
         13 . The apparatus of  claim 12 , wherein the subassembly comprises a cantilevered extension that can prevent the syringe being acted upon. 
     
     
         14 . The apparatus of  claim 1 , wherein the electrodes comprise a conductive metal coated with a conductive, electrochemically stable compound. 
     
     
         15 . The apparatus of  claim 14 , wherein the conductive, electrochemically stable compound is selected from the group consisting of: titanium nitride, platinum, platinum iridium alloys, and iridium oxide. 
     
     
         16 . The apparatus of  claim 1 , wherein a geometry of the predetermined spatial relationship of the electrodes is modifiable. 
     
     
         17 . The apparatus of  claim 3 , wherein the subassembly accepts multiple geometries of the electrodes. 
     
     
         18 . The apparatus of  claim 2 , wherein the applicator comprises a lock that allows an insertion of the subassembly into the applicator only in a priming orientation and prevents an accidental ejection of the subassembly from the applicator in the priming orientation. 
     
     
         19 . The apparatus of  claim 2 , the applicator comprises at least one latch that is operatively connected to the inanimate source of energy to prime the inanimate source of energy when the subassembly is inserted into the applicator. 
     
     
         20 . The apparatus of  claim 2 , the applicator further comprises at least one mechanical stop that is operatively connected to the latch to prevent the latch from disengaging from the inanimate source of energy prior to the deployment of the electrodes.