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 . A drug formulation characterized by a zero shear viscosity of at least 300,000 mPas for injection into the suprachoroidal space of an eye comprising a biologically active substance and a thixotropic polymeric excipient that acts as a gel-like material to spread after injection and uniformly distribute and localize the drug in a region of the suprachoroidal space.  
   
   
       2 . The drug formulation according to  claim 1  further characterized by a viscosity of not more than about 400 mPas at 1000 s −1  shear rate.  
   
   
       3 . The drug formulation according to  claim 1  wherein said gel-like material crosslinks after injection into the suprachoroidal space.  
   
   
       4 . The drug formulation according to  claim 1  wherein said biologically active substance comprises microparticles or microspheres.  
   
   
       5 . The drug formulation according to any one of  claims 1  to  4  wherein said polymeric excipient comprises hyaluronic acid, chondroitin sulfate, gelatin, polyhydroxyethylmethacrylate, dermatin sulfate, polyethylene oxide, polyethylene glycol, polypropylene oxide, polypropylene glycol, alginate, starch derivatives, a water soluble chitin derivative, a water soluble cellulose derivative or polyvinylpyrollidone.  
   
   
       6 . A drug formulation for delivery to the suprachoroidal space of an eye comprising a biologically active substance and microspheres or microparticles with an outer diameter in the range of about 1 to 33 microns  
   
   
       7 . The drug formulation according to  claim 6  further comprising a polymer excipient to uniformly disperse said microspheres or microparticles in the suprachoroidal space.  
   
   
       8 . The drug formulation according  claim 4  or  6  wherein the microparticles or microspheres additionally comprise a controlled release coating.  
   
   
       9 . The drug formulation according to  claim 4  or  6  wherein the microparticles or microspheres additionally comprise a tissue affinity surface.  
   
   
       10 . The drug formulation according to any of  claims 1  to  4  or  6  wherein the biologically active substance comprises an antibiotic, a steroid, a non-steroidal anti-inflammatory agent, a neuroprotectant, an anti-VEGF agent, or a neovascularization suppressant.  
   
   
       11 . The drug formulation of  claim 10  wherein the biologically active substance comprises both a steroid and an anti-VEGF agent or neovascular suppressant.  
   
   
       12 . A device for minimally invasive delivery of a drug formulation into the suprachoroidal space of the eye comprising a needle having a leading tip shaped to allow passage through scleral tissues without damage to the underlying choroidal tissues, and a sensor to guide placement of said tip to deliver said formulation adjacent to or within the suprachoroidal space.  
   
   
       13 . The device according to  claim 12  wherein said sensor provides an image of the scleral tissues.  
   
   
       14 . The device of  claim 12  wherein said sensor responds to ultrasound, light, or differential pressure.  
   
   
       15 . A device for minimally invasive delivery of a drug formulation into the suprachoroidal space of the eye comprising a needle having a leading tip shaped to allow passage through scleral tissues, and an inner tip that provides an inward distending action to the choroid upon contacting the choroid to prevent trauma thereto.  
   
   
       16 . The device according to any one of  claims 12  to  15  further containing a drug formulation comprising a polymeric excipient and a biologically active substance.  
   
   
       17 . The device according to any one of  claims 12  to  15  further comprising a flange to seal the interface between the needle and the interposing tissues.  
   
   
       18 . The device according to any one of  claims 12  to  15  further comprising an angled stop plate located on said device to interface with the outer surface of the eye and set the depth and angle of penetration of said leading tip relative to the eye surface.  
   
   
       19 . A method for administering drugs to eye comprising placing formulation comprising a biologically active substance and a polymer excipient in the suprachoroidal space such that said excipient gels after delivery to localize said biologically active substance.  
   
   
       20 . The method according to  claim 19  wherein said formulation is placed in a posterior region of the suprachoroidal space.  
   
   
       21 . The method according to  claim 19  wherein said formulation is placed in an anterior region of the suprachoroidal space.  
   
   
       22 . A method for administering drugs to a posterior region of the eye comprising placing a formulation comprising a biologically active substance comprising microspheres or microparticles with an outer diameter in the range of about 1 to 33 microns in an anterior region of the suprachoroidal space such that said microspheres or microparticles subsequently migrate to said posterior region.  
   
   
       23 . The method according to  claim 22  wherein said formulation comprises a polymer excipient to uniformly disperse the microparticles or microspheres in the suprachoroidal space.  
   
   
       24 . A method of administering drugs in the suprachoroidal space of the eye comprising the steps of placing a needle in scleral tissues toward the suprachoroidal space at a depth of at least half of the scleral thickness, and injecting a drug formulation through said needle into the sclera such that said formulation dissects the scleral tissues adjacent to said suprachoroidal space and enters said suprachoroidal space.  
   
   
       25 . The method according to any of  claims 19  to  24  wherein said formulation comprises a thixotropic polymer.