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

Abstract

BACKGROUNDDrug 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.METHODSForty‐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.RESULTSThe 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.CONCLUSIONSPMM 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

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

“…29 Existing reports have shown the potential of controlled release systems 30,31 using polymers to avoid the side effects caused due to overdosing and repeated infusion of drug. Although PLGA-based 5-FU-loaded microspheres and implant systems [31][32][33] have shown promising results compared with free drug, the literature still lacks studies evaluating the efficiency of 5-FU particles at the nano level. Nanoparticles possess the ability to permeabilize the cells more efficiently than microspheres due to their smaller size, which facilitates administration of large quantities of drug to give better efficacy.…”

A new generation of anticancer, drug-loaded, colloidal vectors reverses multidrug resistance in glioma and reduces tumor progression in rats

“…For i.c. implantations, 10 3 9L or 5 Â 10 2 F98 cells were injected in the striatum of Fischer rats by stereotaxy at the following coordinates: 0.2 mm posterior from Bregma, 3.0 mm lateral from the sagittal suture, and 5.0 mm below dura as previously described (44).…”

The brain tissue response to biodegradable poly(methylidene malonate 2.1.2)-based microspheres in the rat

“…5-fluorouracil (5-FU) was encapsulated as an ideal candidate for a site-specific sustained release, since it is hydrophilic and potentially toxic systemically. The effectiveness of these microspheres for an intratumoral chemotherapy approach against an established brain tumor was demonstrated [18]. PMM 2.1.2 microspheres degrade slowly in vivo and could constitute an interesting long-term delivery system for the treatment of neurodegenerative diseases.…”