The Anticancer Efficacy and Toxicity of Oral Paclitaxel- Loaded Lipid Nanoparticle in a C3H2 Bladder Cancer Mice.
- Author:
Choong Hyun LEE
1
;
Dong Wan SOHN
;
Hyo Sin KIM
;
Seung Ju LEE
;
Yong Hyun CHO
;
Moon Soo YOON
;
Hesson CHUNG
;
Yeoung Taek PARK
;
Young Wook CHOI
;
Sae Woong KIM
Author Information
1. Department of Urology, College of Medicine, The Catholic University of Korea, Korea. ksw1227@catholic.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Paclitaxel;
Nanoparticle;
Bladder cancer;
Mice
- MeSH:
Absorption;
Animals;
Cell Division;
Cell Line;
Homicide;
Humans;
Mice*;
Microtubules;
Nanoparticles*;
Paclitaxel;
Particle Size;
Polysorbates;
Tumor Burden;
Urinary Bladder Neoplasms*;
Urinary Bladder*
- From:Korean Journal of Urology
2005;46(8):854-860
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Purpose: Paclitaxel is an anticancer drug that blocks cell division by stabilizing microtubules. Even though paclitaxel has been shown to be effective in killing bladder cancer cell lines in vitro, the in vivo absorption was extremely low. A paclitaxel formulation was prepared in solution only, which was bioadhesive, and its effects evaluated in the MBT-2 cell line and in C3H2 bladder cancer mice. In addition, the toxicity of the paclitaxel formulation was also evaluated. Materials and Methods: A muco-adhesive oily paclitaxel formulation was made by the combining of monoolein, tricaprylin, Tween 80 and paclitaxel. MBT-2 cells were cultivated in different concentration of taxol, and the tumoricidal activity measured by the indirect methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay. In an in vivo study, the treatment regimen for the s.c. C3H2 mice was five consecutive once daily administrations, beginning on day 4 post tumor implant. The length and width of the tumors were measured twice a week, and the tumor volume calculated. On day 21, the tumor volume change and toxicity were evaluated. Results: The average particle size of paclitaxel-loaded lipid nanoparticle was about 600nm, with a polydispersity of 1,000. Only 2.6% of the MBT-2 cells were viable after 24 hour of treatment with the formulation at a paclitaxel concentration of 10mug/ml, while showing minimal toxicity of the formulation without paclitaxel. Paclitaxel-loaded lipid nanoparticles, administered orally, allowed significant antitumor activity in C3H2 mice (p<0.05). Conclusions: Paclitaxel-loaded lipid nanoparticles have a remarkable cytotoxic effect against MBT-2 cells, in a dose dependent manner, and the oral paclitaxel-loaded lipid nanoparticle therapy had an inhibitory effect on bladder tumors in a MBT-2 model, but without systemic toxicity. Therefore, oral paclitaxel-loaded lipid nanoparticles may be used for advanced bladder cancer patients.
