Bioadhesive drug delivery system using glyceryl monooleate for the intravesical administration of paclitaxel.
BACKGROUND
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 absorption of intravesically administered paclitaxel in a rabbit model of bladder cancer.


METHODS
Urine, plasma, and tissue pharmacokinetics were determined in rabbits treated for 120 min with paclitaxel (500 microg/20 ml) by intravesical instillation. Two formulations of GMO/paclitaxel were evaluated using different proportions of water, 15 and 30%, and Taxol was used as a control. Animals were observed for clinical signs of toxicity and necropsy was performed.


RESULTS
120 min after instillation, the bladder was emptied and excised. In the urine, paclitaxel concentration was 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 both experimental groups, but 11% in the control group. The concentration then declined exponentially in the underlying capillary-perfused tissues, reaching equilibrium at a depth of 1,400-1,700 microm. The plasma concentrations were extremely low compared with concentrations in urine and bladder tissues and were not associated with clinical toxicity.


CONCLUSIONS
We conclude that GMO has a significantly increased bioadhesiveness to bladder mucosa. Therefore, intravesical administration of GMO/paclitaxel/water provides a significant advantage for drugs targeting the bladder tissue, and paclitaxel represents a viable option for intravesical bladder cancer therapy.
Lee
Seung-Ju
SJ
Department of Urology, College of Medicine, Catholic University, Seoul, Korea.
Kim
Sae Woong
SW
Chung
Hesson
H
Park
Yeong Taek
YT
Choi
Young Wook
YW
Cho
Yong-Hyun
YH
Yoon
Moon Soo
MS
D000042:Absorption; D000283:Administration, Intravesical; D000704:Analysis of Variance; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D016503:Drug Delivery Systems; D005260:Female; D005989:Glycerides / Q000494:pharmacology*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D011817:Rabbits; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000972:Antineoplastic Agents, Phytogenic; D005989:Glycerides; C005953:monoolein; D017239:Paclitaxel