Experimental Transscleral Ocular Drug Delivery: Use of Pluronic F-127 Gel and Fibrin Glue as a Sustained Release System

PURPOSE: The purpose of this study was to evaluate the effect of two sustained release systems (Pluronic F-127 gel and Fibrin glue) on the diffusion of dexamethasone across the human sclera. METHODS: Scleral sections excised from moist-chamber-stored human globes were mounted in a perfusion chamber that can create transscleral pressure. In the sustained release study, sample (100 muL) of 3H-dexamethasone in Pluronic F-127 gel or Fibrin glue was added to the episcleral side of the tissue, while BSS plusR was perfused across the uveal side at an transscleral pressure of 15 mmHg. Perfusate fractions were collected and measured using scintillation spectrometry and scleral permeability was calculated. RESULTS: The apparent permeability constants of the human sclera to 3H-dexamethasone in BSS plus(R) (the control value), Pluronic F-127 gel, and Fibrin glue were 1.15+/-0.11x10(-5) cm/s (n=5), 1.49+/-0.33x10-6 cm/s (n=5), and 7.32+/-0.98x10(-6) cm/s (n=7), respectively. The permeability values of Pluronic F-127 gel and Fibrin glue were relatively lower than the control value. Pluronic F-127 gel and Fibrin glue showed a uniform sustained release characteristic during a 24-hour period. The cumulative release rates of dexamethasone through the human sclera from BSS plus(R) (the control value), Pluronic F-127 gel, and Fibrin glue were 84.0+/-1.5% (n=5), 29.3+/-5.8% (n=5), and 61.5+/-5.9% (n=4) at 20 hours, respectively. There were significant differences in the human scleral permeability constants and cumulative release rates among the three vehicles (p<0.0001). CONCLUSIONS: Pluronic F-127 gel and Fibrin glue provided a slow, uniform sustained release during a 24- hour period. This study established a strong possibility of the new transscleral drug delivery in vitro using the sustained release systems of Pluronic F-127 gel and Fibrin glue. This may be a good experimental tool in the future development of a practical drug delivery system across the sclera for the treatment of a variety of chorioretinal disorders.

The Effect of Transscleral Pressure on Human Scleral Thickness and Hydration

PURPOSE: The purpose of this study was to evaluate the effect of transscleral pressure on the thickness and hydration of the human sclera. METHODS: Scleral sections excised from moist-chamber-stored human globes were mounted in a perfusion chamber that can create transscleral pressure. The scleral thickness was measured at 15-minute intervals using ultrasonic pachymetry with pressure changes of 15, 30, and 60 mmHg every 2 hours. The scleral hydration was measured by maintaining a constant pressure (15, 30, and 60 mmHg) for 4 hours, weighing the hydrated tissue, then drying for 24 hours at 120degrees C, and finally weighing the dry tissue. RESULTS: The changes of scleral thickness from the initial control thickness in the 7-mm perfusion chamber (n=6) were -0.38+/-2.11%, 0.26+/-2.99 %, and -3.92+/-3.40% at 15, 30, and 60 mmHg, respectively. In the 10-mm perfusion chamber (n=5), the thickness changes were -0.56+/-1.35%, -1.05+/-1.63%, and -2.71+/-1.60% at 15, 30, and 60 mmHg, respectively. Scleral thickness was slightly decreased with the increase of transscleral pressure. There was a statistically significant decrease in scleral thickness from 30 mmHg to 60 mmHg in the 7-mm perfusion chamber (p0.10). CONCLUSIONS: The scleral hydration remained essentially unchanged with the transscleral pressure change of 0 ~ 60 mmHg, whereas the scleral thickness showed a slight decrease with the increase of transscleral pressure. Further histologic studies will be needed to assess the ultrastructural change of human sclera in the future.

The mucinous layer of corneal endothelial cells

PURPOSE: The goal of this study was to characterize the morphology of the mucinous layer on rabbit, bovine, owl, and human corneal endothelial cells. METHODS: Corneoscleral buttons were fixed using cetylpyridinium chloride to stabilize "mucus" and the tissue was prepared for transmission electron microscopy. Photomicrographs were measured to determine the thickness of the endothelial and epithelial mucinous layer in the central cornea. RESULTS: The endothelial mucinous layer was seen as a nearly uniform electrodense region on the apical aspect of the endothelium. It was found to be 0.9 microm, 0.9 microm, 0.9 microm, and 0.5 microm thick in rabbit, bovine, owl, and human, respectively. The owl endothelium had an additional less electrodense layer with a granular appearance and a thickness of about 200 microm. The mucinous layer on the epithelium was similar in appearance to that on the endothelium and across species. CONCLUSIONS: The morphologic similarity of the endothelial and epithelial mucinous layers is a serendipitous finding that should prove valuable in experimental design. Ultimately, it is hoped that studies of the posterior corneal surface will deepen our knowledge of endothelial protection.