Abstract
Purpose: :
The purpose of this study was to assess suprachoroidal delivery of beta-blockers, FITC-dextrans (40 and 150 kDa), an MRI contrast agent (Gd-DTPA), and sodium fluorescein (NaF) using LC-MS/MS, spectrofluorometry, noninvasive MRI, and noninvasive Fluorotron spectrofluorometry, respectively.
Methods: :
A mixture of 8 beta-blockers, FITC-dextrans, sodium fluorescein, and Gd-DTPA were injected into the suprachoroidal space of excised New Zealand white rabbit eyes using a 26 G needle with a small tapering head (3/8"). Eyes were incubated in a water bath at 37 0C for up to 3 hours. At the end of 1 and 3 hours, eyes were dissected and various ocular tissues were isolated for beta-blocker and FITC-dextran analysis. For MRI scans rabbit eyes were positioned in an MRI scanner (4.7 T Biospin; Bruker, Billerica, MA) and images were acquired using an adiabatic spin-echo imaging sequence. For sodium fluorescein studies, at 1 and 3 hours following suprachoroidal, intravitreal, or intracameral injections, scans were acquired noninvasively using a Fluorotron Master.
Results: :
Suprachoroidal injections localized the delivery of all solutes largely to the back of the eye, with the drug delivery to the anterior segment being much lower. Beta-blockers as well as FITC-dextrans were localized more to the dosed side when compared to the opposite side in sclera, choroid-RPE, retina, and vitreous. These differences were greater for FITC-dextrans compared to beta-blockers. MRI analysis, while showing drug localization more in the back of the eye tissues, was not sensitive enough to clearly distinguish the differences in tissue drug concentrations between the dosed and undosed sides. With an increase in drug lipophilicity, drug levels in choroid-RPE, retina, and aqueous humor generally increased, with some exceptions. In the vitreous humor, on the other hand, the drug levels declined with an increase in drug lipophilicity. Suprachoroidal injection of sodium fluorescein showed greater signal localization to the choroid and retina at 1 and 3 hours post injection, when compared to intravitreal and intracameral injections.
Conclusions: :
Suprachoroidal injections allow localized delivery to choroid-RPE and retina for small as well as large molecules. Suprachoroidal drug delivery to the vitreous declines with an increase in drug lipophilicity. At least up to 3 hours, drug delivery differs between the dosed and opposite sides following suprachoroidal injections.
Keywords: vitreous • retinal pigment epithelium • choroid