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N.P. Cheruvu, S.P. Ayalasomayajula, U.B. Kompella; Choroid-Tapetum Poses a Significant Barrier to Transscleral Transport and the Retinal Accumulation Following Subconjunctival Administration Does not Depend on Drug Lipophilicity . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4447.
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Purpose: To assess the influence of drug lipophilicity and the presence of choroid-tapetum on transscleral transport in the bovine model and to determine the influence of lipophilicity on ocular disposition following subconjunctival administration in the rat. Methods: The in vitro transport of sodium fluorescein, budesonide, and celecoxib with Log P values of –0.67, 2.20, and 2.48, respectively, was performed using excised bovine sclera with and without choroid-tapetum. Sodium fluorescein, budesonide, and celecoxib were tested at donor concentrations of 100 µM, 100 µg/ml, and 100 µg/ml, respectively, in a buffer containing 5% w/v of hydroxypropyl-ß-cyclodextrin. In the in vivo study, drug (75 µg) solutions with (budesonide and celecoxib) or without (fluorescein) cyclodextrin were injected subconjunctivally in one eye of anesthetized male Sprague Dawley rats, and the animals were sacrificed at the end of 15 min. Budesonide and celecoxib concentrations in sclera, retina, vitreous, lens, and cornea were estimated using a HPLC assay. Fluorescein was estimated using a spectrofluorometer. Results: The percent transport across the sclera in 6 hours was 1.46 (± 0.40), 1.4 (± 1.13), and 1.5 (± 0.52) % for fluorescein, budesonide, and celecoxib, respectively. The percent transport across sclera-choroid-tapetum was 1.26 (± 0.33), 0.03 (± 0.02), and 0.09 (± 0.1) % for fluorescein, budesonide, and celecoxib, respectively. The ipsilateral tissue concentrations (ng/mg) from the in vivo study are shown below. Conclusion: Consistent with earlier reports, the lipophilicity did not influence the scleral permeability. However, the presence of choroid-tapetum reduced the solute flux, with the influence being much greater for the lipophilic drugs. Upon subconjunctival injection, all three drugs reached retina, with no apparent relationship to drug lipophilicity. However, the corneal accumulation of drugs from the subconjunctival route appears to depend on drug lipophilicity. View OriginalDownload SlideView OriginalDownload Slide
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