Porcine sclera as a model of human sclera for in vitro transport experiments: histology, SEM, and comparative permeability

[摘要] Purpose: To evaluate porcine sclera as amodel of human sclera for in vitro studies of transscleral drugdelivery of both low and high molecular weight compounds. Methods: Human and porcine scleras werecharacterized for thickness and water content. The tissue surface wasexamined by scanning electron microscopy (SEM), and the histology wasstudied with hematoxylin-eosin staining. Comparative permeationexperiments were performed using three model molecules, acetaminophenas the model compound for small molecules; a linear dextran with amolecular weight of 120 kDa as the model compound for highmolecular weight drugs; and insulin, which was chosen as the modelprotein. Permeation parameters such as flux, lag time, and permeabilitycoefficient were determined and compared. Results: Human and porcine scleras havea similar histology and collagen bundle organization. The water contentis approx 70% for both tissues while a statistically significantdifference was found for the thickness, porcine sclera beingapproximately twofold thicker than human sclera. Differences inthickness produced differences in the permeability coefficient. Infact, human sclera was found to be two to threefold more permeabletoward the three molecules studied than porcine sclera. Conclusions: The results obtained in thepresent paper prove that porcine sclera can be considered a good modelfor human sclera for in vitro permeation experiments of both low andhigh molecular weight compounds. In fact, if the different tissuethickness is taken into account, comparable permeability wasdemonstrated. This suggests a possible use of this model in theevaluation of the transscleral permeation of new biotech compounds,which currently represent the most innovative and efficient therapeuticoptions for the treatment of ocular diseases.

[学科分类] 生物化学/生物物理