Therapeutic effectiveness of novel 5-fluorouracil-loaded poly(methylidene malonate 2.1.2)-based microspheres on F98 glioma-bearing rats.
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.
Fournier
Elvire
E
Virsol, Paris, France.
Passirani
Catherine
C
Montero-Menei
Claudia
C
Colin
Nathalie
N
Breton
Pascal
P
Sagodira
Serge
S
Menei
Philippe
P
Benoit
Jean-Pierre
JP
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
D008314:Malonates; D011095:Polyethylenes; C091414:poly(methylidene malonate) 2.1.2; D002266:Carboxymethylcellulose Sodium; D005472:Fluorouracil