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A. R. Jani, E. S. Kim, D. E. Berezovsky, R. Kadam, U. B. Kompella, H. F. Edelhauser; Scleral Uptake and Extended Release of Prostaglandin Analogs: Bimatoprost, Latanoprost, and Travoprost in an in vitro Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5967.
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To determine prostaglandin analog (bimatoprost, latanoprost, or travoprost) uptake by the human sclera after a 15 minute exposure on the episclera and then slowly release drug over a course of 24 hours on the choroidal side.
Human donor scleral poles were obtained from the Georgia Eye bank with a mean age ± SD of 51 ± 20 years (range 30 -70) and 2.3 ± 0.6 days post-enucleation to experiment. The scleral tissue was isolated and mounted on a two chamber Lucite block. The episclera was exposed to 200 µL of drug for a period of 15 min before being removed and replaced with BSS. The choroidal side of the tissue was perfused with BSS under 15 mmHg at a flow rate of 3.0µL/min. Scleral tissue from the adjoining sections of the same eye was continuously exposed to the drug for comparison. Perfusate fractions were collected every 2 hrs. Samples were then analyzed by liquid chromatography and tandem mass spectrometry (R2 = 0.9991 for bimatoprost, 0.9975 for latanoprost, and 0.9844 for travoprost).
All three drugs diffused across sclera both with continuous exposure to drug and with a 15 min pulse exposure to the drug. The bimatoprost pulse showed a peak of drug release at the 6 hr sample (as opposed to a peak at the 10 hr sample with continuous exposure) with a gradual decline over 24 hrs. The peak of the pulsed sample was 35.9% that of the continuous sample, and the total drug released in the pulsed samples was 20.2% that of the continuous samples. The latanoprost and the travoprost pulsed samples also showed drug in the perfusate with peak concentrations at 8 and 2 hrs respectively with detectable amounts of drug continuing to be released at 22 and 24 hrs respectively. With all three prostaglandin analogs, there was drug detectable in the tissue even after 24 hrs, though the amount of drug in the pulsed experiment was less than that in the continuous experiment.
This study shows that the sclera can be a reservoir for the prostaglandin analog drugs. The sclera can take up drug after 15 min of exposure and slowly release the drug over 24 hrs with a detectable amount of drug still remaining in the tissue even after 24 hrs. This is suggestive of a role that the sclera may have in the extended effect of action in once a day drug delivery.
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