Influence of Lipophilicity on Transscleral Drug Permeability in Bovine and Porcine Eye Models

Abstract

Abstract: : Purpose: To assess the influence of solute lipophilicity onin–vitro transport across bovine/porcine sclera, bovinesclera–choroid–tapetum, and porcine sclera–choroid.Methods:The in vitro transport of mannitol(H³), sodium fluorescein,budesonide, celecoxib, and rhodamine 6G with Log P values of–3.10, –0.67, 3.20, 3.79 and 4.02, respectively,was performed using freshly excised tissues. Donor solutionsfor in vitro transport studies contained mannitol (1µCi/ml),sodium fluorescein (100 µM), budesonide (100 µg/ml),celecoxib (100 µg/ml), or rhodamine 6G (100 µg/ml)in assay buffer (pH 7.4) containing 5% w/v of hydroxypropyl–ß–cyclodextrinas an adjuvant. Receiver samples were collected at 1, 2, 4 and6 hrs. Solute concentrations were determined using a LiquidScintillation Counter for mannitol (H³), HPLC for budesonideand celecoxib, and spectrofluorometer for sodium fluoresceinand rhodamine 6G. Results: The permeability coefficients (mean± s.d., n = 6) across bovine and porcine tissues aresummarized below: Bovine eye: 

Porcine Eye: 

Conclusion:With an increase in solute lipophilicity, bovineas well as porcine scleral permeability reduced. Solute transportacross sclera–choroid/sclera–choroid–tapetumwas significantly lower compared to scleral transport. The decreasein permeability in the presence of choroid/choroid–tapetumwas significantly higher for lipophilic solutes. Financial Support:Supported by NIH grants DK064172 and EY013842.

Keywords: sclera • choroid • retina