IN-VITRO CYTOTOXICITY OF MACROMOLECULES IN DIFFERENT CELL-CULTURE SYSTEMS

The cytotoxic effect of various macromolecules in cultured bovine brain microvessel endothelial cells, mouse penitoneal macrophages, and rat hepatocytes was analyzed by measuring lactate dehydrogenase (LDH) release and by microscopic observations. Polycations, such as protamine, poly-L-lysine and histone, caused high percentage of LDH-release and significant morphological changes in all cultured cells, whereas other polycations, cationized bovine serum albumin (BSA) and diethylaminoethyl-dextran, showed only a little cytotoxicity. No significant cytotoxic effect was observed in cells incubated with neutral dextran or polyanions involving BSA, its derivatives and dextran sulfate. The present study also demonstrated the difference in sensitivity to toxicity of each macromolecule among different cultured cells: macrophages showed the highest sensitivity among cultured cells used in this study. Thus, we have demonstrated that neutral polymers and polyanions are feasible for safe drug carrier in terms of cytotoxicity. It is also suggested that, depending on the type of polycation, the attention should be paid for using cationic macromolecules in drug delivery systems.