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K. Papangkorn, D. C. Mix, Jr., K. M. Gupta, J. W. Higuchi, B. Brar, S. K. Li, W. I. Higuchi; Transscleral Passive Delivery of Rapamycin in Rabbit Using a Visulex® Topical Application Device. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5318.
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Rapamycin (RAP) is in Phase 1 and 2 clinical trials for multiple ocular indications. The current dosage forms are oral pills that can cause systemic side effects and provide inefficient drug delivery to the eye or ocular injections that may lead to serious complications due to their invasive nature. Previous study has shown that the Visulex® topical application device can noninvasively deliver a therapeutic dose of dexamethasone sodium phosphate into the deeper eye tissues in rabbits. The goal of the present study was to demonstrate that this topical application device could be an alternative for delivery of RAP into the eye.
All studies were performed with New Zealand White rabbits using a Visulex® topical application device. Various formulations were prepared to enhance the solubility of RAP. RAP 100 µL formulation containing 1% oxymetazoline was loaded into a Visulex® topical application device, then applied to the rabbit eye for 30 min. The rabbits were sacrificed at T=0, 4, and 24 h after treatment. RAP in the tissues was extracted with organic solvents and the amount determined by HPLC.
The amount of RAP delivered varied with the formulations. The table shows the amount of RAP delivered into the eye tissues after treatment with a Visulex® device containing a RAP formulation of 88 mg/ml.
RAP delivered into the tissues from Visulex® loaded with the formulation lasted for ~24 h. This suggests RAP presence in the conjunctiva and other ocular tissues at high concentrations as a depot for sustained release over extended period. In experiments with other formulations, RAP delivery up to 180 µg in the eye was observed at T=0 and 4 h.
This study demonstrates that the Visulex® device can passively deliver RAP into the eye and that the drug can remain in the eye tissues for up to 24 h following treatment.
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