Efficacy of paclitaxel released from bio-adhesive polymer microspheres on model superficial bladder cancer

Purpose: We aimed to promote the efficacy of paclitaxel in intracavitary treatment of superficial transitional cell carcinoma of the bladder by designing bio-adhesive microspheres capable of achieving controlled release of the drug at the urothelium/urine interface. Materials and Methods: Poly(methylidene malonate 2.1.2) microspheres encapsulating paclitaxel were prepared by a single emulsion method. Bioactivity of the released paclitaxel was confirmed by assessing cytotoxicity on MBT-2, a bladder cancer cell line. Biodistribution of particles after bladder instillation was assessed by confocal microscopy and scanning electron microscopy. In vivo studies were performed in Balb/c mice after bladder cancer was induced by BBN (N-n-Butyl-N-butan-4-ol-nitrosamine) in drinking water. The efficacy of intravesical injections of conventional and microsphere paclitaxel was assessed by histology and survival rates. Results: Spherical 5 μm microspheres with 5% weight per weight paclitaxel loading ensured sustained release of bioactive paclitaxel. After bladder instillation the microspheres adhered to the mucosa and remained in the bladder lumen for at least 48 hours. In the BBN induced bladder cancer model compared with controls the 9-week survival rate was significantly improved by 2 injections of paclitaxel bio-adhesive microparticles. Microscopic evaluation confirmed the lower incidence of carcinoma in situ and high grade transitional cell carcinoma after injections of paclitaxel bio-adhesive microparticles compared with controls and with injections of similar doses of the conventional paclitaxel formulation. Conclusions: Intravesical administration of poly(methylidene malonate 2.1.2) paclitaxel microspheres is a promising approach for intracavitary chemotherapy of superficial bladder cancer.

Full Text

Duke Authors

Cited Authors

  • Visage, CL; Rioux-Leclercq, N; Haller, M; Breton, P; Malavaud, B; Leong, K

Published Date

  • 2004

Published In

  • Journal of Urology

Volume / Issue

  • 171 / 3

Start / End Page

  • 1324 - 1329

Digital Object Identifier (DOI)

  • 10.1097/01.ju.0000103922.12319.59