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The possibility of developing bioadhesive drug delivery systems on the basis of molecules which selectively bind to the small intestinal epithelium by specific, receptor-mediated mechanisms was investigated using a lectin isolated from tomato fruits (Lycopersicum esculentum). The tomato lectin (TL) was found to bind specifically onto both isolated, fixed pig enterocytes and monolayers of human Caco-2 cell cultures with a similar affinity. TL-coated polystyrene microspheres (0.98 micron) also showed specific binding to enterocytes in vitro. Lectin binding was found to be favored at neutral pH and to be reduced in an acidic environment. Crude pig gastric mucin, however showed a marked cross-reactivity in vitro, indicating that lectin binding to the cell surface in vivo might be inhibited by mucus.