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D. Bucks, T. Lund, G. Winckle, B. Marshall, C. Richardson; An in vitro Model Using Newborn Bovine Eyes to Assess Corneal and Scleral Drug Permeation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5093.
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© ARVO (1962-2015); The Authors (2016-present)
Develop an in vitro corneal and scleral drug permeation model to evaluate ocular drug candidates and ophthalmic formulations applied at clinically relevant exposure levels. Using these methods the permeation of newborn bovine cornea and sclera were compared to rabbit cornea and adult bovine sclera, respectively. The effect of choroid presence on drug permeation of adult bovine sclera was also investigated.
Fresh bovine (newborn [NB] and adult) and rabbit (8–12 weeks old) eyes were obtained from local abattoirs and maintained in moist chamber conditions prior to use. Isolated corneal and scleral tissues were placed in Bronaugh Flow–Thru Diffusion Cells maintained at 35 ºC and dosed with 150 ± 10 mg (∼3 drops) of 10% Aminocaproic Acid (ACA) gel. Receptor phase was pumped through the cells at 1ml/hr. Three in vitro studies were conducted. The first study tested adult bovine scleral permeability in the presence and absence of the choroid membrane. Tissues were perfused with phosphate buffered saline pH 7.4 containing 0.1% sodium azide and 1.5% Oleth–20 for the 3.5 hour duration of exposure. Potential differences between NB and adult bovine sclera devoid of choroid was evaluated in the second study. The third study investigated permeability of rabbit and NB bovine corneas. The latter two studies employed phosphate buffered saline pH 7.4 containing 0.1% sodium azide and 4% BSA as the receptor phase during the 3 hour duration of exposure.
Study #1: Although ACA flux was numerically lower, the presence of choroid did not significantly affect adult bovine scleral ACA flux (p = 0.074, unpaired t–test). The flux of ACA through adult bovine sclera with and without choroid membrane was 2.47 ± 0.75 mg/cm2/hr (31.3 ± 9.8 % of applied dose) and 3.35 ± 0.59 mg/cm2/hr (46.0 ± 9.6 % of applied dose), respectively. Study #2: ACA flux through adult and NB bovine sclera sans choroid membrane was not significantly different (p = 0.87, unpaired t–test). Flux of ACA through adult and NB bovine sclera was 2.58 ± 1.45 mg/cm2/hr (39.9 ± 2.0 % of applied dose) and 2.76 ± 1.36 mg/cm2/hr (40.4 ± 8.6 % of applied dose), respectively. Study #3: Flux of ACA was significantly higher through the cornea of NB bovine relative to rabbit (p = 0.002). Corneal ACA flux from NB bovine and rabbit was 1.30 ± 0.22 mg/cm2/hr (15.0 ± 2.5 % of applied dose) and 0.55 ± 0.20 mg/cm2/hr (6.79 ± 2.4 % of applied dose), respectively.
The cornea and sclera from NB bovine appear to be a promising model to characterize ocular drug permeation.
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