Studies on the retention of the mucous-membrane-adhesive anticancer agent hydroxypropylcellulose doxorubicin.

Abstract

Incorporation of hydroxypropylcellulose (HPC-)doxorubicin, which we developed as a mucous-membrane-adhesive drug preparation, was instilled into the urinary bladder in 10 clinical cases. Tumor of the urinary bladder was a single tumor in all 10 cases, and preclinical histology showed transitional cell carcinoma, grade 1 or 2, and a lower stage than T1. HPC-doxorubicin, 20 mg/20 ml, was administered in 5 cases, and the other 5 cases received the conventional aqueous doxorubicin, 20 mg/20 ml by way of a catheter and the urethra. Cold punch biopsy was performed after 3 days of instillation, and the incorporation of doxorubicin into both tumorous and normal tissue was measured by high-pressure liquid chromatography. After 3 days, it was found that in the HPC-doxorubicin-administered group, doxorubicin was detected in both tumorous and normal tissue, but it was not detected in either tissue after aqueous doxorubicin administration. In 5 cases of the HPC-doxorubicin group, doxorubicin levels in the tumorous and normal tissue were examined, and it was found that significantly more doxorubicin was detected in the tumorous tissues. Thus, it may be said that our HPC-doxorubicin remained longer within the urinary bladder than the conventional aqueous doxorubicin preparation. Instilled HPC-doxorubicin is more highly concentrated in the tumorous tissue than in the normal bladder tissue, and thus, HPC-compounded anticancer drugs may be therapeutically more useful.