Therapeutic effectiveness of novel 5-fluorouracil-loaded poly(methylidene malonate 2.1.2)-based microspheres on F98 glioma-bearing rats.

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.

• Authors: Elvire Fournier, Catherine Passirani, Claudia Montero-Menei, Nathalie Colin, Pascal Breton, Serge Sagodira, Philippe Menei, Jean-Pierre Benoit
• Journal: Cancer (Cancer) Vol. 97 Issue 11 Pg. 2822-9 (Jun 01 2003) ISSN: 0008-543X [Print] United States
• PMID: 12767096 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright 2003 American Cancer Society.

Chemical References

• Malonates
• Polyethylenes
• poly(methylidene malonate) 2.1.2
• Carboxymethylcellulose Sodium
• Fluorouracil

Topics

• Animals
• Biodegradation, Environmental
• Brain Neoplasms (drug therapy)
• Carboxymethylcellulose Sodium
• Drug Delivery Systems
• Female
• Fluorouracil (administration & dosage)
• Glioma (drug therapy)
• Malonates
• Microspheres
• Polyethylenes
• Rats
• Rats, Inbred F344