Abstract Liposomes have been prepared with a polymerised core. Drug release and gastrointestinal (GI) degradation of liposomes with this polymerised core was slightly less important than those of classical liposomes. Vincristine, 5-fluorouracil (5-FU), and methotrexate (MTX) have been incorporated into the liposomes, and studies carried out using the differentiated cell lines Caco-2 and TC7, and with 150 histologically normal sections of human colon. Encapsulation of the drugs in liposomes had variable effects, depending on the test system and the drug used. For 5-FU and MTX calculated to be in a therapeutic range, liposomal formulation enhanced drug permeation, but not for the other drugs tested. In the excised human colon model, the treatment history of the patients can affect bioavailability: pre-operative radiation increased the drug tissue uptake. Transmucosal transport of ions was modified by prior chemotherapy. These results should be taken into account in the design of oral anticancer treatments both at the level of nutritional and pharmacological considerations.