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Craig B Struble, Justine Oswald, Matt Jensson, T Michael Nork; Evaluation of the Trans-Scleral Intravitreous Administration Procedure in Mice and Rats via 3H-Dexran Recovery. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5283.
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© ARVO (1962-2015); The Authors (2016-present)
This study quantitatively assessed the recovery of radioactivity after intravitreous administration of 3H-Dextran (5000kD) to mice and rats
Mice and rats (n=4/group) were anesthetized and a bilateral bolus intravitreous injection of 3H-Dextran (approximately 1 uCi/mL) of 0.5 or 1 µL/eye to mice (Groups 1 and 2, respectively) and 1 or 2 µL/eye to rats (Groups 3 and 4, respectively) was administered to each eye using a trans-scleral procedure. A 30-gauge ½” hypodermic needle made the initial opening into the eye (~ 0.5 to 1 mm from the limbus). The intravitreous dose was administered with a blunt 33-gauge needle attached to a 5-µL Hamilton syringe. The needle was visualized in the vitreous humor prior to injection. A cotton tipped applicator (dose wipe) was gently placed on the eye to recover any of the formulation that leaked from the injection site. At ~10 minutes postdose, the animals were euthanized and whole eyes were collected, rinsed with saline, and gently blotted dry. Dose wipes and eyes were analyzed for radioactivity by liquid scintillation counting.
Mean recovery for a 0.5 µL dose in mouse eyes was 31.9%; ranging from 15.3 to 71.3%. The mean dose wipe was 33.4%. Total recoveries ranged from 25.8% to 81.2%, with a mean of 65.3%. Mean recovery for a 1 µL dose in mouse eyes was 36.0%; ranging from 2.24 to 76.7%. The mean dose wipe was 34.7%. Total recoveries ranged from 26.3% to 88.3%, with a mean of 70.8%. Mean recovery for 1 µL in rat eyes was 49.6%; ranging from 13.7 to 89.1%. The mean dose wipe was 11.4%. Total recoveries ranged from 17.7% to 90.1%, with a mean of 61.0%. Mean recovery for 2 µL in rat eyes was 39.5%; ranging from 13.7 to 66.7%. The mean dose wipe was 26.9%. Total recoveries ranged from 46.6% to 83.5%, with a mean of 66.3%.
Retention of a 3H-Dextran (5000 kD) formulation via trans-scleral intravitreous injection in mouse and rat eyes is highly variable. The data suggests that lower volume doses, 0.5 µL dose in mice and the 1 µL dose in rats, provide a slightly higher retention in the eye. However, in each species, at each dose level, the variability of each dose was high such that determining pharmacokinetic parameters, such as Cmax, would be difficult. Results demonstrate that pharmacokinetic and biodistribution data in rats and mice following an intravitreous dose should be interpreted with caution.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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