Therapeutic effectiveness of novel 5-fluorouracil-loaded poly(methylidene malonate 2.1.2)-based microspheres on F98 glioma-bearing rats
✍ Scribed by Elvire Fournier; Catherine Passirani; Claudia Montero-Menei; Nathalie Colin; Pascal Breton; Serge Sagodira; Philippe Menei; Jean-Pierre Benoit
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 264 KB
- Volume
- 97
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
Abstract
BACKGROUND
Drug delivery to the central nervous system (CNS) remains a real challenge for neurosurgeons and neurologists, because many molecules cannot cross the blood‐brain barrier (BBB). In recent years, solid polymeric materials have been implanted into animal and human brains either by surgery or using stereotactic methods to assure the controlled release of a drug over a determined period, thus circumventing the difficulties posed by the BBB. Poly(methylidene malonate 2.1.2) (PMM 2.1.2) is a new polymer that was described a few years ago and that allows the fabrication of novel, 5‐fluorouracil (5‐FU)‐loaded PMM 2.1.2 microspheres. The objective of the current study was to assess the therapeutic effectiveness of those particles in a rat brain tumor model, the F98 glioma.
METHODS
Forty‐three rats were used in this study. First, a histologic evaluation of the F98 tumor model was performed on Fischer female rats. Thereafter, different groups of rats were injected and were treated with 5‐FU microspheres in 2 different suspension media: carboxymethylcellulose (CMC) aqueous solution with or without 5‐FU.
RESULTS
The tumor was confirmed as extremely aggressive and invasive, even in early development. The 5‐FU‐loaded microspheres improved rat median survival significantly compared with untreated animals, CMC‐treated animals, and 5‐FU solution‐treated animals when injected in CMC without 5‐FU, demonstrating the interest of a sustained release and the efficacy of intratumoral chemotherapy against an established tumor.
CONCLUSIONS
PMM 2.1.2 microspheres appeared to be a promising system, because their degradation rate in vivo was longer compared with many polymers, and they may be capable of long‐term delivery. Cancer 2003;97:2822–9. © 2003 American Cancer Society.
DOI 10.1002/cncr.11388