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S. Lee, C. Durairaj, A. M. Laties, R. S. Kadam, Y. Mo, D. H. Geroski, U. B. Kompella, A. M. McGlinn, H. F. Edelhauser; Transscleral Delivery of Nanoparticle Triamcinolone. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4794.
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To determine the ex vivo and in vivo transscleral permeability of nanoparticle triamcinolone (NTA) compared with commercially available triamcinolone acetonide (TA).
The ex vivo permeability of NTA and TA (1.5 mg/ml) across human donor sclera was tested using a Lucite block perfusion chamber. Levels of NTA diffusing across the sclera were measured every 2 hours for 24 hours using HPLC. Pigmented rabbits (2.2 Kg) were given a subtenon injection in vivo in both eyes with NTA (1.0 mg/ 0.2 ml) or TA (20 mg/0.2 ml). One group (n = 20) of rabbits were euthanized at 2, 4, 6 hours post injection, enucleated, frozen, and dissected into different tissues. The second group of rabbits (n = 20) were euthanized at 2, 4, 6 hours post injection, enucleated, frozen, desiccated, and dissected into different tissues. Each group had a control (n = 4) and immediate euthanasia subgroups (IE) (n = 4) which were enucleated at 6 hours post injection. Drug concentration in the dissected tissues was measured using HPLC.
Ex vivo NTA had a faster transscleral permeability constant (Kconst) of 1.09 ± 0.42 x 10-5 cm/s compared to TA at 5.93 ± 2.90 x 10-9 cm/s. After 6 hours, retina/choroid level of TA was 3.78 ± 2.31 ng/mg and 1.91 ± 0.59 ng/mg with NTA. Vitreous level was 0.24 ± 0.22 ng/ml with TA and 9.73 ± 5.14 ng/ml with NTA after 6 hours. In dessicated eyes, TA concentration in the retina was 1.94 ± 0.65 ng/ml without immediate euthanasia (IE) and 34.89 ± 6.68 ng/mg with IE. TA concentration in the choroid was 12.71 ± 5.59 ng/mg without IE and 26.98 ± 4.44 ng/mg with IE at 6 hours.
Both TA and NTA are able to diffuse across human and rabbit sclera. The retina/choroid concentration is comparable in both TA and NTA, however, NTA showed higher vitreous concentration with a small dose. Based on the dry desiccated tissue data, the choroid is a major barrier in transscleral drug delivery of TA and NTA.
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