The effect of ocular pigmentation on transscleral delivery of triamcinolone acetonide.

PURPOSE: To determine the capacity and kinetics of the binding between triamcinolone acetonide (TA) and the ocular pigment for a better understanding of the transscleral delivery.
METHODS: In the in vitro study, natural melanin (sepia officinalis, Sigma-Aldrich) was incubated at 37°C with different concentrations of TA and the binding capacity/binding affinity was measured. The TA releasing profile from the melanin was also studied through repeated incubation of TA-melanin in fresh phosphate-buffed saline. In the ex vivo study, the effect of the choroidal pigment on the trans sclera/choroid permeability of TA was investigated through Franz-type vertical diffusion cells using both a TA suspension and a saturated TA solution.
RESULTS: The amount of TA bound to melanin increases with the increase of the TA concentration and with an increase in the incubation time. A Scatchard analysis revealed that the maximum number of moles of TA bound to melanin is predicted to be 22.43 nmol/mg, with a binding affinity of K=2.4×10(-5) nM(-1). TA released from a pigment showed a fast phase within the first 24 h and a slow phase thereafter. About 40% of the bound TA released in the first day and 73.94% of accumulative release was observed after 5 days. The TA suspension showed more TA penetration through the scleral-choroid complex than the saturated solution (P=0.0104). The apparent permeability coefficients for the suspension across the sclera-choroid of pigmented and albino rabbits are 7.48±1.53×10(-6) cm/s and 10.78±2.49×10(-6) cm/s, respectively.
CONCLUSIONS: TA can bind to and release from the ocular pigment, which may extend the TA ocular half-life and therapeutic duration when TA is delivered through a subtenon injection. A further in vivo study is warranted to validate the findings and to quantitate the magnitude of the difference between pigmented and albino animals.