Implantable devices and methods for evaluation of active agents

Abstract

Devices for the local delivery of microdose amounts of one or more active agents, alone or in combination, in one or more dosages, to selected tissue of a patient are described. The devices generally include multiple microwells arranged on or within a support structure and contain one or more active agents, alone or in combination, in one or more dosages and/or release pharmacokinetics. In an exemplary embodiment, the device has a cylindrical shape, having symmetrical wells on the outside of the device, each well containing one or more drugs, at one or more concentrations, sized to permit placement using a catheter, cannula, or stylet. Optionally, the device has a guidewire, and fiber optics, sensors and/or interactive features such as remote accessibility to provide for in situ retrieval of information and modification of device release properties. In a preferred embodiment, the fiber optics and/or sensors are individually accessible to discrete wells.

We claim: 
     
         1 . An implantable microdevice comprising:
 a support structure having microwells on a surface of or formed within the support structure; optionally including a compound release mechanism for controlling the release of an active agent from the microwells;   wherein the device is configured to permit implantation into a tissue using a catheter, cannula or biopsy needle, and   wherein the device is further configured to release one or more active agents from the microwells to separate and discrete areas of tissue adjacent to the microwell.   
     
     
         2 . The microdevice of  claim 1 , comprising an active agent release mechanism selected from the group consisting of the dimensions of an opening into the microwells, a film, a membrane, a polymer matrix, and a hydrogel pad. 
     
     
         3 . The microdevice of  claim 1  further comprising one or more active agent or combinations of active agent within the microwells. 
     
     
         4 . The microdevice of  claim 3  wherein the active agent or combinations thereof are present in different amounts. 
     
     
         5 . The microdevice of  claim 3  having microwells with different pharmacokinetic release profiles. 
     
     
         6 . The microdevice of  claim 3 , wherein the active agent is selected from the group consisting of cancer therapeutics, anti-angiogenic agent, immunomodulator, and anti-infective agents. 
     
     
         7 . The microdevice of  claim 1  further comprising a guide wire, wherein the guidewire is mechanically coupled to the microdevice support structure. 
     
     
         8 . The microdevice of  claim 1 , wherein the microwells are separated by walls or include recessions which limit release of active agents into areas of release from adjacent microwells. 
     
     
         9 . The microdevice of  claim 1 , wherein the microdevice comprises biodegradable polymers. 
     
     
         10 . The microdevice of  claim 1  wherein active agent is released from the microwells as a bolus, sustained release, delayed release, bolus followed by sustained release, and/or pulsatile release. 
     
     
         11 . The microdevice of  claim 1  wherein the active agent is present in solid form in the reservoir. 
     
     
         12 . The microdevice of  claim 1  wherein the device does not comprise needles or a fluid reservoir. 
     
     
         13 . The microdevice of  claim 1  formed of a plastic selected from the group consisting of polyether-ether-ketone, polysulfone and polyphenylsulfone. 
     
     
         14 . The microdevice of  claim 1  formed by methods selected from the group consisting of deep ion etching, nano imprint lithography, micromachining, laser etching, three dimensional printing and stereolithography 
     
     
         15 . A kit comprising the microdevice of  claim 1  and means for implantation and removal selected from the group consisting of a catheter, cannula and biopsy needle having an inner diameter slightly larger than the outer diameter of the microdevice and at least one layer of cells from the tissue into which it is to be implanted. 
     
     
         16 . A method for determining efficacy of a compound in vivo or in situ comprising implanting using a catheter, cannula or biopsy need inserted into a tissue within an organism an implantable microdevice comprising:
 a support structure having microwells on a surface of or formed within the support structure, the microwells each containing and releasing after implantation one or more active agents selected from the group consisint of therapeutic, prophylactic and diagnostic agents, the microwells optionally including a compound release mechanism for controlling the release of an active agent from the microwells;   wherein the device is configured to permit implantation into a tissue using a catheter, cannula or biopsy needle, and   wherein the device is further configured to release one or more active agents from the microwells to separate and discrete areas of tissue adjacent to the microwell.   
     
     
         17 . The method of  claim 16 , wherein the microdevice comprises an active agent release mechanism selected from the group consisting of the dimensions of an opening into the microwells, a film, a membrane, a polymer matrix, and a hydrogel pad. 
     
     
         18 . The method of  claim 16  wherein the microdevice comprises two or more active agents, dosages of active agents or combinations of active agent within the microwells. 
     
     
         19 . The method of  claim 16  wherein the microdevice has microwells releasing active agent with different pharmacokinetic release profiles. 
     
     
         20 . The method of  claim 16  wherein the microdevice is implanted using a catheter and a guide wire, wherein the guidewire is mechanically coupled to the support structure of the microdevice. 
     
     
         21 . The method of  claim 16  wherein the microwells of the microdevice are separated by walls or include recessions which limit release of active agents into areas of release from adjacent microwells. 
     
     
         22 . The method of  claim 16  wherein active agent is released from the microwells as a bolus, sustained release, delayed release, bolus followed by sustained release, and/or pulsatile release. 
     
     
         23 . The method of  claim 16  wherein the active agent is present in solid form in the reservoir or the device does not comprise needles or a fluid reservoir. 
     
     
         24 . The method of  claim 16  wherein the microdevice is formed by methods selected from the group consisting of deep ion etching, nano imprint lithography, micromachining, laser etching, three dimensional printing and stereolithography. 
     
     
         25 . The method of  claim 16  further comprising evaluating drug efficacy in vivo or in situ by removing the microdevice and an amount of surrounding tissue after an amount of time. 
     
     
         26 . The method of  claim 25  further comprising cutting the surrounding tissue along an axis parallel to a length of the microdevice to form a slab of tissue to be analyzed. 
     
     
         27 . The method of  claim 25 , wherein the microdevice is removed using a coring needle. 
     
     
         28 . The method of  claim 25 , wherein the thickness of the removed tissue is approximately 500 μm. 
     
     
         29 . The method of  claim 25 , wherein the assay is performed in vivo without removal of the tissue adjacent to the microdevice. 
     
     
         30 . The method of  claim 25 , wherein the assay is performed in situ after removing the device and adjacent tissue from the organism. 
     
     
         31 . The method of  claim 16 , wherein the tissue is a tumor.