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

Cancer. 2003 Jun 1;97(11):2822-9. doi: 10.1002/cncr.11388.


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.

Publication types

  • Comparative Study

MeSH terms

  • 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


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