Transscleral Permeability of Calcitriol, a new potential treatment for Retinoblastoma

Abstract

Abstract: : Background:Systemic administration of calcitriol has been demonstrated to cause a greater than 50% inhibition of retinoblastoma as compared to the controls in a mouse model. Use of this treatment in children has not been undertaken because of the associated toxicity related to hypercalcemia. Transscleral delivery of these agents has the potential to inhibit tumor growth without systemic toxicity. Purpose:To determine the in vitro scleral permeability of calcitriol. Methods:Scleral sections excised from moist-chamber stored human globes were mounted in a perfusion chamber. Transscleral pressure was maintained at 15 mm Hg and temperature was kept at 37 degrees Celsius. A small depot of drug (5.68 x 10-2 nanomoles/ml 3H-Calcitriol in BSS) was placed on the episcleral surface. BSS was perfused to the choroidal side for 24 hours. Fractions of choroidal perfusate were collected and radioactivity was measured with a scintillation counter. From this data, scleral permeability Ktrans (cm/sec) was calculated. Results:Ktrans for 3H-Calcitriol was 8.89 +/- 3.34 x 10-8 (mean +/- SE, n=8). Semi steady state was reached at 2 hours with a peak value of 3.88 x 10-6 nanomoles/ml reached at 3 hours. Conclusion:This study shows that delivery of 3H-Calcitriol in a physiologic solution across the human sclera can be achieved. Transscleral drug delivery of this drug for the treatment of retinoblastoma could possibly deliver higher intraocular concentrations than systemically and minimize side effects.

Keywords: 569 retinoblastoma • 514 pharmacology • 574 sclera