Compositions and methods for localized therapy of the eye

Abstract

Compositions, and methods of using such compositions, useful for injection into the posterior segments of human or animal eyes are provided. Such compositions include small particles of a poorly soluble therapeutic agent that facilitates formation of concentrated regions of the therapeutic agent in the retinal pigmented epithelium of an eye. The particles are formed by combining a therapeutic agent with an ophthalmically acceptable polymer component. The particles have sizes less than about 3000 nanometers, and in some cases, less than about 200 nanometers. One example of a composition includes particles of triamcinolone acetonide and hyaluronic acid have a size less than about 3000 nanometers.

1 . A pharmaceutical composition for placement in a posterior segment of an eye of a living human or animal, the composition comprising: 
 a therapeutic component comprising a poorly soluble therapeutic agent in the form of particles having a size effective to form concentrated regions of the therapeutic agent in the retinal pigmented epithelium (RPE) of the eye which are effective to provide a desired therapeutic effect to the human or animal when the composition is administered to a posterior segment of an eye of a human or animal.    
     
     
         2 . The composition of  claim 1 , wherein the particles have a size effective to form concentrated regions having a concentration of the therapeutic agent that is greater relative to the concentration of the therapeutic agent in the composition when administered to the eye.  
     
     
         3 . The composition of  claim 1 , wherein the particles are sized to be distributed in the eye to reduce toxicity associated with the therapeutic agent in an anterior tissue of the eye.  
     
     
         4 . The composition of  claim 1 , wherein the particles comprise the therapeutic agent and a polymer suitable for administration to the posterior segment of an eye.  
     
     
         5 . The composition of  claim 1 , further comprising a polysaccharide component positioned relative to the particles to stabilize the particles.  
     
     
         6 . The composition of  claim 5 , wherein the polymer is hyaluronic acid.  
     
     
         7 . The composition of  claim 1 , wherein the particles have an average size effective to promote phagocytosis of the particles by the RPE.  
     
     
         8 . The composition of  claim 1 , wherein the particles have an average size effective to promote pinocytosis by the RPE.  
     
     
         9 . The composition of  claim 1  wherein the therapeutic agent is formed as particles having an effective average particle size less than about 3000 nanometers.  
     
     
         10 . The composition of  claim 1  wherein the therapeutic agent is formed as particles having an effective average particle size of less than about 500 nanometers.  
     
     
         11 . The composition of  claim 1  wherein the therapeutic agent is formed as particles having an effective average particle size of less than about 400 nanometers.  
     
     
         12 . The composition of  claim 1  wherein the therapeutic agent is formed as particles having an effective average particle size of less than about 200 nanometers.  
     
     
         13 . The composition of  claim 1  wherein the therapeutic component comprises a first population of particles having an effective average particle size of less than about 200 nanometers, a second population of particles having an effective average particle size in a range of about 200 nanometers to less than 400 nanometers, and a third population of particles having an effective average particle size in a range of about 400 nanometers to less than about 3000 nanometers.  
     
     
         14 . The composition of  claim 1  wherein the therapeutic agent has a solubility in water at 25° C. of less than about 10 mg/ml.  
     
     
         15 . The composition of  claim 1  wherein the therapeutic agent comprises a corticosteroid.  
     
     
         16 . The composition of  claim 1  which further comprises an effective amount of a pharmaceutically acceptable vehicle component.  
     
     
         17 . The composition of  claim 16  wherein the vehicle component is aqueous-based.  
     
     
         18 . The composition of  claim 16  wherein the therapeutic agent is present in an amount of up to about 25% (w/v) of the composition.  
     
     
         19 . A pharmaceutical composition for placement in a posterior segment of an eye of a living human or animal, the composition comprising: 
 a therapeutic component comprising a poorly soluble steroid in the form of particles sized and distributed in the composition to form concentrated regions of the steroid in the retinal pigmented epithelium (RPE) of the eye which are effective to provide a desired therapeutic effect to the human or animal when the composition is administered to a posterior segment of an eye of a human or animal.    
     
     
         20 . The composition of  claim 19  wherein the therapeutic component comprises a corticosteroid.  
     
     
         21 . The composition of  claim 19 , wherein the therapeutic component comprises a first population of particles containing a poorly soluble steroid, and a second population of particles containing the poorly soluble steroid, the second population having an effective average particle size that is different than the first population.  
     
     
         22 . The composition of  claim 19 , wherein the particles have a size from about 200 nanometers to about 3000 nanometers.  
     
     
         23 . The composition of  claim 19 , further comprising an ophthalmically acceptable vehicle component.  
     
     
         24 . An ophthalmically acceptable composition comprising a population of particles including triamcinolone acetonide having an effective average particle size less than about 3000 nanometers.  
     
     
         25 . The composition of  claim 24 , wherein the population of particles has an effective average particle size less than about 500 nanometers.  
     
     
         26 . The composition of  claim 24 , wherein the population of particles has an effective average particle size less than about 200 nanometers.  
     
     
         27 . The composition of  claim 24 , comprising a first population of particles including triamcinolone acetonide, and a second population of particles including triamcinolone acetonide having an effective average particle size that is different from an effective average particle size of the first population.  
     
     
         28 . The composition of  claim 24 , further comprising an ophthalmically acceptable vehicle component.  
     
     
         29 . The composition of  claim 24 , wherein the particles comprise a combination of triamcinolone acetonide and an ophthalmically acceptable polymer component.  
     
     
         30 . The composition of  claim 24 , further comprising a polymer component positioned relative to the particles to stabilize the particles.  
     
     
         31 . The composition of  claim 30 , wherein the polymer component is hyaluronic acid.  
     
     
         32 . The composition of  claim 24 , wherein the particles are sized to be distributed in the eye to reduce toxicity associated with the triamcinolone acetonide in an anterior tissue of the eye.  
     
     
         33 . The composition of  claim 24 , wherein the particles are sized to form one or more concentrated regions of triamcinolone acetonide in the retinal pigment epithelium of an eye.  
     
     
         34 . A population of particles comprising triamcinolone acetonide having an effective average particle size less than about 3000 nanometers.  
     
     
         35 . The particles of  claim 34  provided in a liquid carrier component.  
     
     
         36 . The particles of  claim 35  provided in a dispensing apparatus.  
     
     
         37 . The particles of  claim 34 , wherein the particles comprise a combination of triamcinolone acetonide and hyaluronic acid.  
     
     
         38 . The particles of  claim 34 , wherein the particles have a size effective to facilitate transfer of the particles into the retinal pigmented epithelium (RPE) when the particles are administered to an eye.