Distribution of doxorubicin in the bladder wall and regional lymph nodes after bladder submucosal injection of liposomal doxorubicin in the dog

PURPOSE: Liposome-encapsulated doxorubicin (Lip-Dox) has increased therapeutic efficacy and reduced toxicity compared to free doxorubicin (Dox). To assess the utility of Lip-Dox for local control of bladder cancer, we examined the distribution of Dox in the bladder wall and the regional lymph nodes of dogs after bladder submucosal injection of Lip-Dox. MATERIALS AND METHODS: In 8 dogs (group SM), Lip-Dox (2 mg.:1 ml.) was injected into the submucosal layer of each lateral bladder wall by using a flexible cystoscope. The other 8 dogs (group IV) underwent intravenous injection of free Dox (4 mg.). Both groups of animals were sacrificed at 1, 3, 5 or 7 days after the injections. The concentration of Dox was measured in both the mucosal and muscle layers of 5 bladder wall sites and also in the external iliac lymph nodes bilaterally. RESULTS: The Dox-concentration in the lymph nodes of group SM was significantly higher (about 15-100 times) than that of group IV throughout the whole follow-up period. The Dox-concentration in the bladder wall for group SM was significantly higher than that in group IV (about 70-930 times at the lateral walls and 2-830 times at the other sites). CONCLUSION: The present results demonstrate that Lip-Dox injected into the bladder submucosally distributes well, both in the whole bladder wall and in regional lymph nodes and remains at a high concentration in these tissues for at least one week after injection.