Abstract
A collagen vitrigel membrane (CVM) we developed can function as both a scaffold for cells and a pathway for chemicals. To extrapolate the corneal permeability of chemicals in vivo, we proposed six corneal models using the CVM. Thin and thick CVMs were utilized as models for Bowman's membrane (BM) and an acellular-stroma (AS), respectively. Models for a corneal epithelium (CEpi), a corneal epithelium-acellular stroma (CEpi-AS), a corneal epithelium-endothelium (CEpi-Endo) and a corneal epithelium-acellular stroma-endothelium (CEpi-AS-Endo) were fabricated by culturing corneal epithelial cells and/or corneal endothelial cells on the surface of CVMs. Subsequently, the permeability coefficient (Papp) value of each model was calculated using five chemicals with different molecular radii; cyanocobalamin and four FITC-dextrans (FD-4, FD-10, FD-20 and FD-40). The slopes of Papp versus molecular radii of those chemicals in the both BM and AS models were almost similar to data using an excised rabbit corneal stroma. The ratios of Papp values in models for BM, CEpi and CEpi-Endo against those in data using an excised rabbit cornea were calculated as 75.4, 6.4 and 4.5-folds for FD-4 and 38.7, 10.0 and 4.2-folds for FD-10, respectively. Similarly, those in models for AS, CEpi-AS and CEpi-AS-Endo were calculated as 26.1, 2.5 and 0.6-folds for FD-4 and 26.1, 1.5 and 0.6-folds for FD-10, respectively. These results suggest that the CEpi-AS-Endo model with both the barrier function of corneal cell layers and the diffusion capacity of chemicals in thick CVM is most appropriate for extrapolating the corneal permeability of chemicals in vivo.
- cell models
- distribution
- drug absorption
- in vitro-in vivo prediction (IVIVE)
- membrane permeability
- organotypic models
- The American Society for Pharmacology and Experimental Therapeutics