Diminished genotoxicity of mitomycin C and farmorubicin included in polybutylcyanoacrylate nanoparticles

doi:10.1016/0027-5107(92)90085-G

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis

Volume 268, Issue 1, July 1992, Pages 77-82

https://doi.org/10.1016/0027-5107(92)90085-G Get rights and content

Abstract

The genotoxic effects of mitomycin C (MMC) and farmorubicin (FR) in a free form and included in polybutlycyanoacrylate nanoparticles (PBCN) were studied employing the Salmonella/microsome mutagenicity assay and the micronucleus test in mouse bone marrow as well as in mouse fetal liver. The data obtained clearly indicated that MMC (0.25–2.00 μg/plate) was a strong mutagen in S. typhimurium TA102, while the same concentrations of this compound in PBCN were ineffective in inducing his⁺ revertant mutations in bacterial cells. A similar total suppression of mutagenic activity of FR (1.0–20.0 μg/plate)was registered in S. typhimurium TA98 when the drug was included in PBCN. Furthermore, the incorporation of MMC (2.0 or 4.0 mg/kg, i.p.) into PBCN strongly diminished or even abolished its clastogenic activity in the bone marrow of virgin and pregnant mice as well as in mouse fetal liver, respectively. In addition, a lack of genotoxic effect of PBCN only was also established. The toxic activity of MMC in mouse bone marrow was significantly reduced or completely abolished after its inclusion in PBCN.

A conclusion might be drawn that the genotoxic activity of some antitumor drugs might be markedly diminished or even abolished after their incorporation in PBCN.

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The initial drug concentration did not have a large effect on the average particle size, which was within the ranges 230–270 nm (Fig. 5a). This size was much smaller than the size of EPI-PBCA particles (465 nm) prepared previously at similar conditions (polymerization of the monomer in aqueous medium containing D40, citric acid and 0.2 mg/ml of drug) but without using acetone [25]. Our preliminary studies demonstrated that polymerization under similar conditions, but without acetone, could also result in the formation of stable nanoparticles, but large aggregates and micron-sized droplets of non-dispersed monomer were obtained simultaneously (data not shown).
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Nevertheless, no chemical reactions (such as polymerization) take place during the formation of colloids by nanoprecipitation, which is another advantage, because the contact between drug molecules and highly reactive monomers is avoided. However, to the best of the authors’ knowledge, all previous studies on anthracycline-loaded PACA formulations have been carried out with particles prepared by polymerization-based methods [17–19]. Here, we extend and adapt the nanoprecipitation approach (as alternative to the classical polymerization-based methods) and try to shed new light on the preparation and in vitro evaluation of PBCA colloidal nanospheres loaded with epirubicin.
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Diminished genotoxicity of mitomycin C and farmorubicin included in polybutylcyanoacrylate nanoparticles

Abstract

Eur. J. Cancer

Mutation Res.

Mutation Res.

Mutation Res.

J. Controlled Release

Enhancement of adriamycin antitumor activity by its binding with an intracellular sustained-release form, polymethacrylate nanospheres, in U-937 cells

Cancer Res.