PERMEABILITY OF MACROMOLECULES IN CULTURED ENDOTHELIAL AND TUMOR-CELL LAYERS ON MICROPOROUS MEMBRANES

The permeation characteristics of macromolecules were studied in layers of bovine aortic endothelial cells (EC) and human colon adenocarcinoma SW-1116 cells (SW-1116) cultured on fibronectin-coated polycarbonate membranes. EC monolayer and SW-1116 layers which consisted of two to four cell layers at confluency were considered as models for vascular wall and tumor tissue, respectively. The studies using [C-14]sucrose (Mw: 342), [C-14]inulin (Mw: 5000), and [C-14]dextran (T-70) (Mw: 70 000) showed that both cell layers functioned as size-selective barriers and the permeability coefficients for SW-1116 were larger than those for EC by a factor of 1.5. Permeation and association with the cell layers were evaluated for radiolabeled charged macromolecules with the same molecular weight (70 000), including derivatives of dextran and bovine serum albumin (BSA) and macromolecular prodrugs of mitomycin C (MMC), MMC-dextran conjugates (MMCD). Both anionic and cationic macromolecules had lower permeability coefficients in both cell layers compared with neutral dextran. On the other hand, neutral and anionic macromolecules showed almost no interaction with the cell layers whereas cationic macromolecules were significantly associated with both of the cell layers. These findings suggest that cationic macromolecules would exhibit low permeability across the cell layers because of electrostatic interaction with the negative charges of the cells, while the permeation of anionic macromolecules might be restricted by electric repulsion. The present study, thus, clarified the permeability characteristics of macromolecules at the cellular level.