Bioadhesive Drug Delivery System for the Intravesical Administration of Paclitaxel in Rabbits

Lee, Seung Ju; Kim, Sae Woong; Lee, Choong Bum; Kang, Seong Hak; Cho, Yong Hyun; Yoon, Moon Soo

Abstract

PURPOSE: Many reports have shown that the efficacy of intravesical therapy for bladder cancer is, in part, limited by the poor penetration of drugs into the urothelium. The present study evaluated the effect of glyceryl monooleate (GMO) on the delivery and penetration of paclitaxel into the bladder of rabbits, when given as an intravesical dose.
MATERIALS AND METHODS
The urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120min with paclitaxel (500g/20ml) by an intravesical instillation. Two formulation of GMO/paclitaxel were evaluated, according to the proportion of water, 15% and 30%, with Taxol was used as a control. The animals were observed for clinical signs of toxicity, and necropsy performed.
RESULTS
At 120min post-instillation, the bladders were emptied and excised. The urine paclitaxel concentrations were decreased by 39.6 and 41.2% in the two experimental groups, and by 25.2% in the control group. The paclitaxel concentrations in the urothelium were 53 and 56% of the urine concentration in the two experimental groups, respectively, but by only 11% in the control group. The concentration then declined exponentially in the underlying capillary perfused tissues, reaching equilibrium at a depth of 1,400-1,700um. The plasma concentrations were extremely low compared with those in the urine and bladder tissues, and were not associated with clinical toxicity.
CONCLUSIONS
These results indicate that GMO improves the delivery of paclitaxel and increases the concentration in the bladder tissue. These results suggest that the intravesical delivery of GMO/paclitaxel/water provide a significant bladder tissue targeting advantage, and that paclitaxel represents a viable candidate drug for intravesical bladder cancer therapy.