Topical cyclosporine-containing formulations and uses thereof

Abstract

Provided herein are formulations for topical ophthalmic formulations containing 0.087-0.093 wt % of cyclosporine, and methods of making and using such formulations. In some aspects and embodiments the formulations may include a polyoxyl lipid or fatty acid, and/or a polyalkoxylated alcohol and may include nanomicelles. Also included herein are methods of treating or preventing diseases or conditions, such as ocular diseases or conditions.

1 .- 31 . (canceled) 
     
     
         32 . An ophthalmic nanomicellar solution formulation comprising about 0.087 wt % to about 0.093 wt % encapsulated cyclosporine, wherein the nanomicelles have a particle size of about 5 nm to about 50 nm, and wherein the formulation has a pH of about 5 to about 8. 
     
     
         33 . The ophthalmic nanomicellar solution formulation of  claim 32 , wherein the formulation has an entrapment efficiency of cyclosporine of about 100%. 
     
     
         34 . The ophthalmic nanomicellar solution formulation of  claim 32 , wherein the formulation is stable at 40° C. 
     
     
         35 . The ophthalmic nanomicellar solution formulation of  claim 32 , wherein the formulation has a pH of about 6.6 to about 7. 
     
     
         36 . The ophthalmic nanomicellar solution formulation of  claim 32 , wherein the nanomicelles have a particle size of about 10 nm to about 40 nm. 
     
     
         37 . The ophthalmic nanomicellar solution formulation of  claim 32 , wherein the nanomicelles have a particle size of about 15 nm. 
     
     
         38 . The ophthalmic nanomicellar solution formulation of  claim 32 , wherein the formulation comprises about 0.09 wt % cyclosporine. 
     
     
         39 . A method of increasing tear production in a subject suffering from keratoconjunctivitis sicca, the method comprising topically administering to the eye an ophthalmic nanomicellar solution formulation twice daily, wherein the formulation comprises about 0.087 wt % to about 0.093 wt % encapsulated cyclosporine, nanomicelles particle size of about 5 nm to about 50 nm, and pH of about 5 to about 8. 
     
     
         40 . The method of  claim 39 , wherein the tear production is measured by a Schirmer test score from baseline. 
     
     
         41 . The method of  claim 39 , wherein the ophthalmic composition comprises about 0.09 wt % cyclosporine. 
     
     
         42 . The method of  claim 39 , wherein the formulation has a pH of about 6.6 to about 7. 
     
     
         43 . The method of  claim 39 , wherein the nanomicelles have a particle size of about 10 nm to about 40 nm. 
     
     
         44 . The ophthalmic nanomicellar solution formulation of  claim 43 , wherein the nanomicelles have a particle size of about 15 nm. 
     
     
         45 . The method of  claim 39 , wherein the ophthalmic composition demonstrates a clinically significant improvement in tear production with >10 mm increase in Schirmer test score from baseline. 
     
     
         46 . A method of treating keratoconjunctivitis sicca in a subject, the method comprising topically administering to the eye an ophthalmic nanomicellar solution formulation comprising about 0.09% wt cyclosporine twice daily, wherein the formulation shows an early onset in clinical improvement compared to other formulations of cyclosporine A. 
     
     
         47 . The method of  claim 46 , wherein formulation demonstrates clinically significant improvement in tear production in tear production with ≥10 mm increase in Schimer test score from baseline. 
     
     
         48 . The method of  claim 46 , wherein nanomicelles have a particle size of about 10 nm to about 40 nm. 
     
     
         49 . The method of  claim 48 , wherein the nanomicelles have a particle size of about 15 nm. 
     
     
         50 . The method of  claim 46 , wherein the formulation has a pH of about 5 to about 8. 
     
     
         51 . The method of  claim 50 , wherein the formulation has a pH of about 6.6 to about 7. 
     
     
         52 . A method of treating an anterior ocular condition, the method comprising administering an ophthalmic nanomicellar solution formulation comprising about 0.087 to about 0.093 wt % cyclosporine, wherein the composition has a pH of about 5 to about 8, and nanomicelles have a particle size of about 5 nm to about 50 nm. 
     
     
         53 . The method of  claim 52 , wherein the anterior ocular condition is dry eye. 
     
     
         54 . The method of  claim 52 , wherein the ophthalmic nanomicellar solution formulation is administered twice daily. 
     
     
         55 . The method of  claim 52 , wherein the ophthalmic composition comprises about 0.09 wt % cyclosporine.