Visual Indication of Rupture of Drug Reservoir

Abstract

Devices and methods are provided for visualizing the opening of a drug reservoir of an implantable medical device. The disclosure provides methods for observing the release or exposure of contents from a drug reservoir of a medical device placed within the vitreous of an eye of a subject. The methods include implanting a drug delivery device within an anatomy of a subject. The device includes a plurality of reservoirs, each loaded with a therapeutic agent and a marker, and a plurality of barrier layers for separating the contents of the reservoirs from the anatomy. The method further includes irradiating at least one of the barrier layers such that at least one of the reservoirs is breached, thereby triggering release of the therapeutic agent and the marker from the device. By visually detecting release of the marker into the anatomy, release of the therapeutic agent into the anatomy is verified.

What is claimed is: 
     
         1 . A drug delivery device for implantation into an eye, the drug delivery device comprising:
 a first reservoir configured to be loaded with a first therapeutic agent;   a first marker associated with the first therapeutic agent; and   a barrier layer of the first reservoir, wherein the barrier layer extends circumferentially around the first reservoir,   wherein the first reservoir is configured, in response to absorption by a first optical radiation at the barrier layer, to release the first therapeutic agent and the first marker, wherein the first marker indicates the release of the first therapeutic agent.   
     
     
         2 . The drug delivery device of  claim 1 , wherein the drug delivery device is a rod-like structure. 
     
     
         3 . The drug delivery device of  claim 1 , further comprising:
 a plurality of reservoirs, wherein each reservoir is configured to be loaded with a therapeutic agent, wherein each reservoir has a barrier layer, wherein each barrier layer extends circumferentially around its respective reservoir, and wherein each reservoir is configured, in response to an optical radiation at its respective barrier layer, to release the therapeutic agent and a marker associated with the therapeutic agent to indicate the release of the therapeutic agent.   
     
     
         4 . The drug delivery device of  claim 3 , wherein each reservoir of the plurality of reservoirs are configured to receive the optical radiation independent of the other reservoirs of the plurality of reservoirs. 
     
     
         5 . The drug delivery device of  claim 1 , further comprising a visual indication associated with the first reservoir for identifying the first reservoir. 
     
     
         6 . The drug delivery device of  claim 5 , wherein the visual indication includes a plurality of markings, wherein each marking is located on the device so that at least one marking is visible by a user of a device applying the optical radiation. 
     
     
         7 . The drug delivery device of  claim 6 , wherein the plurality of marking are circumferentially positioned around the first reservoir. 
     
     
         8 . The drug delivery device of  claim 1 , wherein the drug delivery device is configured to be free-floating within the eye after implantation. 
     
     
         9 . The drug delivery device of  claim 1 , which is configured to release the first marker from the first reservoir into an ocular region prior to release of the first therapeutic agent from the reservoir into the ocular region. 
     
     
         10 . The drug delivery device of  claim 1 , wherein the first marker is unbound from the first therapeutic agent. 
     
     
         11 . The drug delivery device of  claim 1 , wherein the first marker comprises a coating on an internal surface of the first reservoir. 
     
     
         12 . The drug delivery device of  claim 1 , further comprises a second marker arranged spatially in the first reservoir with the first therapeutic agent and the first marker. 
     
     
         13 . The drug delivery device of  claim 1 , wherein the first marker is a fluorophore. 
     
     
         14 . The drug delivery device of  claim 13 , wherein the fluorophore is selected from the group consisting of fluorescein, rose Bengal, indocyanine green, and rhodamine. 
     
     
         15 . The drug delivery device of  claim 1 , wherein the first therapeutic agent is selected from the group consisting of anti-inflammatories, anti-infectives, anti-allergens, cholinergic agonists and antagonists, adrenergic agonists and antagonists, anti-glaucoma agents, agents for cataract prevention or treatment, neuroprotection agents, anti-oxidants, antihistamines, anti-platelet agents, anti-coagulants, anti-thrombic agents, anti-scarring agents, anti-proliferatives, anti-tumor agents, complement inhibitors, decongestants, vitamins, growth factors, anti-growth factor agents, gene therapy vectors, chemotherapy agents, protein kinase inhibitors, small interfering RNAs, limus family compounds, and combinations thereof. 
     
     
         16 . The drug delivery device of  claim 1 , wherein the first therapeutic agent comprises an anti-vascular endothelial growth factor (anti-VEGF) agent. 
     
     
         17 . The drug delivery device of  claim 16 , wherein the anti-VEGF agent is selected from the group consisting of aflibercept (VEGF trap), bevacizumab (AVASTIN), pegaptanib sodium (MACUGEN), and ranibizumab (LUCENTIS). 
     
     
         18 . A drug delivery device for implantation into an eye, the drug delivery device comprising:
 a first reservoir loaded with a first therapeutic agent; and   a barrier layer extending circumferentially around the first reservoir,   wherein the first reservoir is configured, in response to absorption by a first optical radiation at the barrier layer, to generate or expose a visual indicator upon breach of the first reservoir, the visual indicator being visibly observable with visible light to verify exposure of the first therapeutic agent to an ocular region.   
     
     
         19 . The drug delivery device of  claim 18 , wherein the visual indicator comprises an air bubble. 
     
     
         20 . The drug delivery device of  claim 18 , wherein the visual indicator comprises a hole in the barrier layer. 
     
     
         21 . The drug delivery device of  claim 18 , wherein the visual indicator comprises a predetermined color of the barrier layer, and wherein the predetermined color indicates a ruptured barrier layer. 
     
     
         22 . The drug delivery device of  claim 18 , wherein the visual indicator is a shape of the barrier layer. 
     
     
         23 . A drug delivery device for implantation within or adjacent an ocular region of a subject, comprising:
 a plurality of reservoirs each loaded with a therapeutic agent and a marker; and   a plurality of barrier layers each separating contents of one of the reservoirs from the ocular region, each barrier layer being arranged to receive a selected exposure to irradiation effective to breach the barrier layer and thereby trigger release of the marker from one of the reservoirs associated with the breached barrier layer,   wherein the marker released into the ocular region is observable with visible light in order to verify exposure of the therapeutic agent to the ocular region.   
     
     
         24 . The drug delivery device of  claim 23 , wherein the marker is unbound from the therapeutic agent.