title: 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.affiliation: Virsol, Paris, France.
authors.forename: Elvire
authors.initials: E
authors.lastname: Fournier
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
authors.forename: Claudia
authors.initials: C
authors.lastname: Montero-Menei
authors.forename: Nathalie
authors.initials: N
authors.lastname: Colin
authors.forename: Pascal
authors.initials: P
authors.lastname: Breton
authors.forename: Serge
authors.initials: S
authors.lastname: Sagodira
authors.forename: Philippe
authors.initials: P
authors.lastname: Menei
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benoit
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental; D001932:Brain Neoplasms / Q000188:drug therapy*; D002266:Carboxymethylcellulose Sodium; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005910:Glioma / Q000188:drug therapy*; D008314:Malonates; D008863:Microspheres; D011095:Polyethylenes; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D008314:Malonates; D011095:Polyethylenes; C091414:poly(methylidene malonate) 2.1.2; D002266:Carboxymethylcellulose Sodium; D005472:Fluorouracil