Antitumour activity and adverse reactions of combined treatment with chitosan and doxorubicin in tumour-bearing mice

We examined the antitumour activity and adverse reactions, such as myelotoxicity, gastrointestinal toxicity and body‐weight loss, of the cancer chemotherapy drug doxorubicin when given with chitosan in sarcoma 180‐bearing mice. Intraperitoneally administered doxorubicin (5 mg kg−1) given on days 1 and 8 with or without orally administered chitosan (200, 400 and 800 mg kg−1 twice daily) inhibited tumour growth. The orally administered chitosan (400 and 800 mg kg−1 twice daily) prevented doxorubicin‐induced body‐weight loss and small‐intestinal mucosal injury. Similarly, the reduction of leucocyte number induced by the intraperitoneally administered doxorubicin was restored to normal by the oral administration of chitosan (400 and 800 mg kg−1 twice daily). It seems likely that the mechanisms by which the orally administered chitosan protects against doxorubicin‐induced gastrointestinal toxicity may be due to the formation of doxorubicin‐chitosan complex in the small‐intestinal mucosa through the diffusion of chitosan into the small‐intestinal villi. In conclusion, our data suggest that the oral administration of chitosan prevents the gastrointestinal mucositis associated with doxorubicin therapy.