Purchase this article with an account.
A. Thakur, R. Kadam, U. B. Kompella; Affinity of Various Corticosteroids to Bovine Lens, Trabecular Meshwork, Choroid-RPE, and Sclera. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5161.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Since corticosteroids are implicated in cataract development and elevated intraocular pressure, one objective of this study was to determine the binding of these drugs to lens and trabecular meshwork. Since transscleral drug delivery is a potential approach to treat back of the eye disorders, another objective of this study was to determine the affinity of corticosteroids to sclera, choroid-RPE, and melanin. These affinities were assessed as a function of drug lipophilicity.
n-octanol-PBS (pH 7.4) partition coefficient (Log D) at 37 °C was determined for triamcinolone, prednisolone, dexamethasone, fluocinolone acetonide, triamcinolone acetonide, and budesonide, using shake flask method. Drug partitioning from PBS into bovine lens, trabecular meshwork, sclera and choroid-RPE was assessed at 37 °C over 6 h. All the corticosteroids were used as a cocktail of drugs for partitioning study. At the end of incubation, PBS was separated after centrifugation and tissues were washed with PBS. A liquid extraction method was used for drug extraction from tissues. The in vitro melanin binding was determined using natural melanin (Sepia Officinalis). All buffer and tissue samples were analyzed for drug content using an LC/MS/MS method.
Log D of the above corticosteroids ranged from 0.7 to 3. Drug extraction with ethyl acetate resulted in extraction efficiencies in the range of 90 to 110%. Tissue:buffer partition ratio was 0.7-1.4, 2.3-7.8, 1.7-11.3, and 10.2-29, respectively, for lens, trabecular meshwork, sclera, and choroid-RPE, respectively. All corticosteroids bind to natural melanin with a binding affinity ranging from 0.35-7.3 µM and binding capacity ranging from 2.1-7.2 µmoles/mg melanin. In general, the tissue partitioning and melanin binding showed a positive correlation with Log D. The correlations further improved, when Log P (obtained using SciFinder Scholar) instead of Log D was used. Additionally, melanin binding showed positive correlation with tissue partitioning.
Possibly due to melanin binding, choroid-RPE exhibited the highest affinity for corticosteroids. Hydrophilic lens exhibited the least affinity for corticosteroids. Sclera as well as trabecular meshwork discriminated the steroids the most and these tissues have significant affinities for corticosteroids, although less than choroid-RPE.
This PDF is available to Subscribers Only