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Saffar Mansoor, Samirkumar R. Patel, Cetin Tas, Hans E. Grossniklaus, Henry F. Edelhauser, Mark R. Prausnitz; Pharmacokinetics and Biodistribution of Triamcinolone Acetonide Following Suprachoroidal Injection into the Rabbit Eye In Vivo Using a Microneedle. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6585.
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As an alternative to intravitreal injection, this study presents injection of traimcinolone acetonide (TA) into the suprachoroidal space (SCS) using a hollow microneedle. This minimally invasive approach deposits TA between the sclera and choroid, which targets TA delivery to its therapeutic site of action. The purpose of this study is to quantify the pharmacokinetics and biodistribution of TA in the rabbit eye. This is the first study to assess sustained drug delivery in vivo after injection into the SCS using a microneedle.
TA (Triesence, 2000 µg/100 µl) was injected into the SCS of pigmented rabbits using a metal microneedle measuring 700-800 µm in length inserted 5 mm posterior to the limbus. Rabbits were euthanatized and eyes were enucleated at 30 min, 7 days, 30 days, 60 days and 120 days following SCS injection. Ocular tissues (sclera, choroid, retina, vitreous, anterior chamber, lens and optic nerve) were separated. TA was then extracted and quantified using HPLC. The safety of SCS injections was assessed by histopathology.
The percent TA recovered from the eyes was 95.3±1.6% at 30 min after injection, which decayed with a half life of 39 days to a value of 11.64±1.5% after 120 days. The distribution of TA in ocular tissues at 30 min after injection was 82.5% in choroid, 17.5% in sclera and 0% in retina, vitreous, anterior chamber, lens and optic nerve. After 120 days, the distribution of TA was 70.3% in choroid, 18.5% in sclera, 6.0% in retina, 4.7% in vitreous, 0.2% in anterior chamber, 0.2% in lens and 0.1% in optic nerve. Histopathological examination of ocular tissues at 7 days showed no significant differences compared to untreated companion eyes. The SCS injections were well tolerated and no rabbits experienced adverse events.
Biodistribution analysis showed that sclera, choroid and retina concentrations of TA accounted for approximately 95% of the total drug in the eye at all time points, indicating excellent drug targeting. Choroidal levels of TA were the highest at all time points. Pharmacokinetic analysis demonstrated elevated levels of TA in the SCS for at least 120 days, showing the potential for sustained delivery to the posterior segment in a minimally invasive way. Histopathology suggested that SCS injection was safe.
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