Methods for drug delivery

Abstract

Methods and devices for delivering an agent to a solid tissue in vivo for assessment of efficacy are described. One method involves withdrawing of a needle from and injecting of the agent into the solid tissue; another method involves delivering the agent using a plurality of microdialysis probes to a solid tissue.

What is claimed is: 
     
         1 .- 135 . (canceled) 
     
     
         136 . An implantable microdevice comprising:
 a support structure having on the surface thereof a plurality of microwells formed on or within the support structure,   the device having dimensions that permit implantation into a tissue using a catheter, cannula, or biopsy needle,   optionally comprising a guidewire attached to a proximal end of the device, one or more sensors integrated within the device or microwells, and fiber optic or other addressible or interactive means for remote interrogation of the device.   
     
     
         137 . The microdevice of  claim 136 , comprising one or more active agents within the microwells. 
     
     
         138 . The microdevice of  claim 137 , comprising a plurality of active agents, combinations of active agents or active agents with plurality of concentrations or release pharmacokinetics thereof. 
     
     
         139 . The microdevice of  claim 136 , wherein the device is cylindrical in shape and having a diameter of between about 0.5 mm and about 2.0 mm, and a length of less than about 5.0 mm. 
     
     
         140 . The microdevice of  claim 136 , formed by a method selected from the group consisting of lithographic galvanoforming abforming (LIGA), high-aspect-ratio photolithography using a photoresist, microelectro-discharge machining, high-aspect-ratio machining by deep reactive ion etching (DIRE), hot embossing, 3-dimensional printing, stereolithography, laser machining, ion beam machining, and mechanical micro-cutting. 
     
     
         141 . The microdevice of  claim 136 , comprising a guidewire attached to an end of the device, one or more sensors integrated within the device or microwells, and fiber optic or other addressable or interactive means for remote interrogation of the device. 
     
     
         142 . The microdevice of  claim 136 , comprising means for maintaining tissue in a spatial orientation to the microdevice at the time of or after removal of the device. 
     
     
         143 . A kit comprising the microdevice of  claim 136  and means for insertion or means for removal. 
     
     
         144 . The kit of  claim 143 , wherein the microdevice comprises one or more active agents within the microwells. 
     
     
         145 . The kit of  claim 144 , wherein the microdevice comprises a plurality of active agents, combinations of active agents or active agents with plurality of concentrations or release pharmacokinetics thereof. 
     
     
         146 . The kit of  claim 143 , wherein the microdevice comprises a guidewire attached to an end of the device, one or more sensors integrated within the device or microwells, and fiber optic or other addressable or interactive means for remote interrogation of the microdevice. 
     
     
         147 . The kit of  claim 143 , wherein the microdevice comprises means for maintaining tissue in a spatial orientation to the microdevice at the time of or after removal of the microdevice. 
     
     
         148 . The kit of  claim 143 , wherein the means for insertion is a biopsy cutting needle between 19 and 24 gauge. 
     
     
         149 . The kit of  claim 143 , wherein the means for removal is a biopsy coring needle between 16 and 18 gauge. 
     
     
         150 . The kit of  claim 143 , wherein the device comprises a guidewire attached to an end of the device, one or more sensors integrated within the device or microwells, and fiber optic or other addressable or interactive means for remote interrogation of the device, comprising means for interacting or receiving signals from the microdevice. 
     
     
         151 . A method for assaying tissue for an effective active agent, effective dosage, effective pharmacokinetics of an active agent, or a combination thereof, comprising implanting in a tissue the microdevice of  claim 136  and assaying for at least one analyte or removing tissue for analysis. 
     
     
         152 . The method of  claim 151 , comprising removing the microdevice and adjacent tissue and analyzing the tissue. 
     
     
         153 . The method of  claim 151 , wherein the tissue is a tumor. 
     
     
         154 . The method of  claim 151 , wherein the tissue is infected or in need of immunomodulation or hormonal treatment. 
     
     
         155 . An implantable microdevice comprising:
 a support structure having on the surface thereof a well formed within the support structure,   the device having dimensions that permit implantation into a tissue using a needle,   optionally comprising a guide attached to the device or an array controller means for remote interrogation of the device.   
     
     
         156 . The microdevice of  claim 155 , comprising one or more active agents within the well. 
     
     
         157 . The microdevice of  claim 155 , comprising combinations of active agents or active agents with plurality of concentrations. 
     
     
         158 . The microdevice of  claim 155 , comprising one or more of a position marker, positioning mechanism, or block device for maintaining tissue in a spatial orientation to the microdevice at the time of insertion of said device into said tissue or after removal of the device. 
     
     
         159 . An implantable microdevice comprising:
 (i) a structure comprising one or more microdialysis probes having on the surface thereof a membrane; wherein the device is configured to permit implantation of said one or more microdialysis probes into a solid tissue using one or more needles of said device;   (ii) optionally a guiding device configured to guide the insertion of said one or more needles comprising said microdialysis probe into said tissue, wherein said guiding device is selected from the group consisting of: a positioning mechanism, a depth-control mechanism, and a needle withdrawal mechanism; and   (iii) optionally a controller.   
     
     
         160 . The microdevice of  claim 159 , comprising one or more agents within the microdialysis probe. 
     
     
         161 . The microdevice of  claim 159 , comprising a plurality of agents or agents at different concentrations. 
     
     
         162 . The microdevice of  claim 159 , comprising one or more of a position marker, positioning mechanism, or block device for maintaining tissue in a spatial orientation to the microdevice at the time of insertion of said device into said tissue or after removal of the device.