Efficacy of Paclitaxel-Loaded Bioadhesive Drug Deliver System Based on Glyceryl Monooleate Nanoparticle in an Orthotopic Murine Bladder Cancer Model

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

Abstract

Purpose
The purpose of this study was to evaluate the efficacy of paclitaxel-loaded glyceryl monooleate (GMO) in the intravesical treatment of superficial transitional cell carcinomas of the bladder by enhancing the bioadhesiveness and bioavailability.
Materials and Methods
A mucoadhesive oily paclitaxel formulation was prepared using GMO, tricaprylin, Tween(8) 80 and paclitaxel. The bioactivity of the GMO/paclitaxel formulation was confirmed by assessing its cytotoxicity on MBT-2, a bladder cancer cell line. An in vivo study was performed in C3H2 mice after induction of bladder cancer by an intravesical bladder tumor implantation. The efficacy of the intravesical administration of the GMO/paclitaxel was assessed by the histology and bladder weight.
Results
The average particle size of the GMO/paclitaxel was 600nm. Only 2.6% of the MBT-2 cells were viable after 24 hours of treatment with GMO/paclitaxel at a paclitaxel concentration of 10microgram/ml. In the orthotopic bladder cancer model the tumor incidence rate was significantly decreased by intravesical administration of the GMO/paclitaxel compared to the controls. The average bladder weight of the GMO/paclitaxel group was significantly lower than that of controls. No toxicity was observed in either of the groups.
Conclusions
Intravesical administration of the GMO/paclitaxel formulation had an inhibitory effect on the bladder tumor in an orthotopic bladder cancer model. This formulation may be a promising approach for intravesical chemotherapy of superficial bladder cancer.