[Studies on enhancement of drug absorption through the bladder mucosa]

We examined the effects of dimethyl sulfoxide (DMSO), hyaluronidase and saponin on drug absorption through the bladder mucosa. Female Wistar rats underwent intravesical instillation of each agent prior to the administration of lanthanum solution or anticancer drug; 4'-O-tetrahydropyranyldoxorubicin (THP). The absorption of lanthanum was recognized as dense grain in bladder tissue under electron microscope. The concentration of THP in bladder tissue and plasma was measured by high performance liquid chromatography. The ultrastructural change caused by instillation of DMSO, hyaluronidase and saponin was also investigated by transmission and scanning electron microscopy. The electron microscopic study of the bladder treated with DMSO revealed the exfoliation of superficial cells, and the electron-dense grains of lanthanum were observed in submucosal layer. The concentration of THP was twice as high as that of untreated animals in both bladder tissue and plasma. The treatment with hyaluronidase caused no severe histological change of bladder mucosa, and lanthanum was observed only in the cytoplasma of superficial cells. The increased concentration of THP was slightly exhibited in plasma but not in bladder tissue. The treatment with saponin caused vacuolization and swelling of superficial cells, and many grains of lanthanum were observed between superficial cells and intermediate cells. The concentration of THP in bladder tissue was significantly higher than that of untreated animals, but in plasma no difference was revealed. These findings indicate that each three agent caused an unique effect on drug absorption of bladder mucosa and such characteristic of each agent must be considered for clinical application. Saponin is thought to be useful on intravesical chemotherapy because of increased concentration of anticancer drug (THP) in bladder tissue without that in plasma.