Abstract
Abstract: :
Background:Developing more effective methods of drug delivery to the posterior segment of the eye is important to improving the treatment of posterior segment eye disease. Delivering drugs into the sclera is safer and less invasive than intraocular delivery and additionally offers the potential for localized drug delivery. It also minimizes the risk of side effects associated with systemic delivery of drugs for posterior segment eye disease. Purpose:To determine the in vitro intrascleral delivery and permeability of a fluorescein labeled oligonucleotide. 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 the compound (5 ul of 1.49 x 10-4 fluorescein labeled oligonucleotide, MW=8286.5) was injected into the sclera at an approximate depth of 80% thickness using an intra-scleral delivery device. 100 ul of BSS was placed on the episcleral surface at the start of the experiment. BSS was perfused to the choroidal side for 24 hours. Fractions of choroidal perfusate were collected and fluorescence was measured with a spectrofluorometer. From this data, scleral permeability Ktrans (cm/sec) was calculated. Results:Ktrans for the fluorescein labeled oligonucleotide was 1.32 +/- 0.42 x 10-7 (mean +/- SE, n=4) A peak value of 3.16 x 10-11 nanomoles/ml was reached at 1 hour. 33.26 +/- 7.02%, 27.03 +/- 7.43%, and 17.75 +/- 4.05% (mean +/- SE) of the moles were collected in the receiver chamber, tissue, and donor chamber respectively. Conclusion: Intrascleral injection of compounds/drugs is a new technique that has not been well studied. This study shows that the delivery of a small volume of a fluorescein labeled oligonucleotide injected into the human sclera can be achieved. Intrascleral delivery of compounds/drugs could utilize smaller volumes and minimize systemic side effects. Intrascleral delivery of compounds/drugs such as DNA may be well suited to this technique for treatment of posterior segment disease.
Keywords: 574 sclera • 419 gene transfer/gene therapy • 514 pharmacology