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

Abstract

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.