Apparatus and formulations for suprachoroidal drug delivery

Abstract

Drug formulations, devices and methods are provided to deliver biologically active substances to the eye. The formulations are delivered into scleral tissues adjacent to or into the suprachoroidal space without damage to the underlying choroid. One class of formulations is provided wherein the formulation is localized in the suprachoroidal space near the region into which it is administered. Another class of formulations is provided wherein the formulation can migrate to another region of the suprachoroidal space, thus allowing an injection in the anterior region of the eye in order to treat the posterior region.

1 - 25 . (canceled) 
     
     
         26 . A method of administering a therapeutic substance to a suprachoroidal space (SCS) of an eye, comprising:
 inserting a distal end portion of a puncture member of a medical injector into a pars plana region of the eye until the distal end portion of the puncture member reaches the SCS, the puncture member defining a lumen therethrough;   with the distal end portion of the puncture member disposed within the SCS of the eye, advancing a flexible cannula distally through the lumen of the puncture member, beyond the distal end portion of the puncture member and along SCS towards a posterior region of the eye, the flexible cannula having an atraumatic distal tip and defining a lumen therethrough; and   with the distal tip of the flexible cannula disposed within the SCS beyond the distal end portion of the puncture member, administering the therapeutic substance to the SCS such that the therapeutic substance is advanced posteriorly in the SCS and away from the distal tip of the flexible cannula.   
     
     
         27 . The method of  claim 26 , wherein:
 during the advancing, illuminating the SCS via the flexible cannula to verify disposal of the flexible cannula in the SCS.   
     
     
         28 . The method of  claim 27 , wherein verification of the flexible cannula in the SCS is based on visual observation of a reduction in intensity of reflective light observed at a surface of the eye, the reduction in intensity at the surface indicating that the distal tip of the flexible cannula has advanced from a sclera of the eye and into the SCS. 
     
     
         29 . The method of  claim 26 , wherein the flexible cannula is disposed in the lumen of the puncture member proximal to the distal end portion during the inserting. 
     
     
         30 . The method of  claim 26 , wherein the flexible cannula includes a lubricious coating to aid in its advancement. 
     
     
         31 . The method of  claim 26 , wherein the puncture member is a needle having a gauge between about 20 to about 25. 
     
     
         32 . The method of  claim 26 , further comprising a luer connector at a proximal end portion of the medical injector to facilitate transfer of the therapeutic substance. 
     
     
         33 . The method of  claim 26 , wherein the theraperutic substance comprises an antibiotic, a steroid, a non-steroidal anti-inflammatory agent, a neuroprotectant, an anti-VEGF agent, or a neovascularization suppressant. 
     
     
         34 . The method of  claim 26 , wherein the therapeutic substance is administered in a drug formulation comprising a microparticles or microspheres. 
     
     
         35 . The method of  claim 34 , wherein the microparticles or microspheres comprise at least one of a controlled release coating or a tissue affinity surface. 
     
     
         36 . The method of  claim 26 , wherein the therapeutic substance is administered in a drug formulation formulated for sustained release over time. 
     
     
         37 . The method of  claim 26 , wherein the therapeutic substance is administered in a drug formulation formulated to control the distribution of the therapeutic substance. 
     
     
         38 . The method of  claim 26 , wherein the therapeutic substance is administered in a drug formulation comprising a polymeric excipient. 
     
     
         39 . The method of  claim 38 , wherein the polymeric excipient comprises hyaluronic acid, chondroitin sulfate, gelatin, polyhydroxyethylmethacrylate, dermatin sulfate, polyethylene oxide, polyethylene glycol, polypropylene oxide, polypropylene glycol, polyvinylpyrollidone, polyvinylalcohol, alginate, gelatin, starch derivatives, a water soluble chitin derivative, a water soluble cellulose derivative, dermatin sulfate, glycosaminoglycans, or a mixture thereof. 
     
     
         40 . A method for treating inflammation or macular edema comprising administering to a subject in need thereof a drug formulation comprising a steroid, the method comprising:
 inserting a distal end portion of a puncture member of a medical injector into a pars plana region of the eye until the distal end portion of the puncture member reaches the SCS, the puncture member defining a lumen therethrough;   with the distal end portion of the puncture member disposed within the SCS of the eye, advancing a flexible cannula distally through the lumen of the puncture member, beyond the distal end portion of the puncture member and along SCS towards a posterior region of the eye, the cannula having an atraumatic distal tip and defining a lumen therethrough; and   with the distal tip of the flexible cannula disposed within the SCS beyond the distal end portion of the puncture member, administering the therapeutic substance to the SCS such that the therapeutic substance is advanced posteriorly in the SCS and away from the distal tip of the flexible cannula.   
     
     
         41 . The method of  claim 40 , wherein:
 during the advancing, illuminating the SCS via the flexible cannula to verify disposal of the flexible cannula in the SCS.   
     
     
         42 . The method of  claim 41 , wherein verification of the flexible cannula in the SCS is based on visual observation of a reduction in intensity of reflective light observed at a surface of the eye, the reduction in intensity at the surface indicating that the distal tip of the flexible cannula has advanced from a sclera of the eye and into the SCS. 
     
     
         43 . The method of  claim 40 , wherein the flexible cannula is disposed in the lumen of the puncture member proximal to the distal end portion during the inserting. 
     
     
         44 . The method of  claim 40 , wherein the flexible cannula includes a lubricious coating to aid in its advancement. 
     
     
         45 . The method of  claim 40 , wherein the puncture member is a needle having a gauge between about 20 to about 25. 
     
     
         46 . A method for treating macular degeneration comprising administering to a subject in need thereof a drug formulation comprising an anti-VEGF compound or neovascular suppressant, the method comprising:
 inserting a distal end portion of a puncture member of a medical injector into a pars plana region of the eye until the distal end portion of the puncture member reaches the SCS, the puncture member defining a lumen therethrough;   with the distal end portion of the puncture member disposed within the SCS of the eye, advancing a flexible cannula distally through the lumen of the puncture member, beyond the distal end portion of the puncture member and along SCS towards a posterior region of the eye, the cannula having an atraumatic distal tip and defining a lumen therethrough; and   with the distal tip of the flexible cannula disposed within the SCS beyond the distal end portion of the puncture member, administering the therapeutic substance to the SCS such that the therapeutic substance is advanced posteriorly in the SCS and away from the distal tip of the flexible cannula.   
     
     
         47 . The method of  claim 46 , wherein:
 during the advancing, illuminating the SCS via the flexible cannula to verify disposal of the flexible cannula in the SCS.   
     
     
         48 . The method of  claim 47 , wherein verification of the flexible cannula in the SCS is based on visual observation of a reduction in intensity of reflective light observed at a surface of the eye, the reduction in intensity at the surface indicating that the distal tip of the flexible cannula has advanced from a sclera of the eye and into the SCS. 
     
     
         49 . The method of  claim 46 , wherein the flexible cannula is disposed in the lumen of the puncture member proximal to the distal end portion during the inserting. 
     
     
         50 . The method of  claim 46 , wherein the flexible cannula includes a lubricious coating to aid in its advancement. 
     
     
         51 . The method of  claim 46 , wherein the puncture member is a needle having a gauge between about 20 to about 25.