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Exp Eye Res. 2004 Mar;78(3):599-607.

Drug delivery through the sclera: effects of thickness, hydration, and sustained release systems.

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1
Emory Eye Center, Emory University, Suite B2600, 1365B Clifton Road, NE, Atlanta, GA, USA.

Abstract

The purpose of this study was to determine whether trans-scleral pressure affects scleral solute permeability by altering scleral thickness or hydration, and to investigate the sustained release delivery of dexamethasone. Scleral sections from donor human globes were mounted for in vitro flux studies. Scleral thickness and hydration were measured as functions of trans-scleral pressure. For the sustained release studies, 3H-dexamethasone in pluronic F-127 gel or in fibrin sealant was added to the episcleral side of the tissue and flux studies were performed. While scleral thickness showed a tendency to decrease with increasing pressure, a significant decrease in thickness was measured only at a trans-scleral pressure of 60 mmHg. No significant changes in scleral hydration were measured over the range of trans-scleral pressures studied. The apparent permeability constants (Ktrans) of human sclera for 3H-dexamethasone in BSS plus, fibrin sealant and F-127 gel were 11.5 x 10(-6), 7.3 x 10(-6), and 1.5 x 10(-6) cm sec(-1), respectively. Human scleral permeability to dexamethasone differed significantly among the three vehicles (p < 0.0001). Cumulative delivery of dexamethasone from BSS plus, F-127 gel, and fibrin sealant were 85.0, 29.3, and 67.9% at 20 hr, respectively. Scleral hydration was unaffected by trans-scleral pressures. Scleral thinning was only observed at 60 mmHg. Trans-scleral pressures below 60 mmHg would not be expected to significantly affect the permeability of the tissue to solutes in the size range of conventional drugs. F-127 gel and fibrin sealant provided a slow, relatively uniform sustained release through a 24 hr period. These systems might be employed to achieve sustained therapeutic levels of drugs to the posterior segment of eye.

PMID:
15106940
[Indexed for MEDLINE]

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