Controlled release of methotrexate from w/o microemulsion and its in vitro antitumor activity.

The objective of this study was to prepare the microemulsion of methotrexate (M-MTX) for oral use and to investigate the suppressive effect of MTX-loaded microemulsion on MCF-7 human breast cancer cells. At the same time this effect of M-MTX was compared with those of a solution of the drug (Sol-MTX). Microemulsion was composed of soybean oil as oil phase, a mixture of Cremophore EL and Span 80 as surfactants, and isopropyl alcohol as co-surfactant, and 0.2 N NaOH as the aqueous phase. MTX was added into microemulsion at the last stage. We clearly demonstrated that M-MTX had a significant cytotoxic effect on breast cancer cell lines and the cytotoxic effect of M-MTX was significantly more than that of solutions (p < 0.05) and IC(50) value for M-MTX was 40 ng/mL. We also examined M-MTX and Sol-MTX on a model biological environmental model. For this purpose a gastrointestinal cell culture model, the Caco-2 cell line, was used to investigate the cytotoxic effects of the polymeric carrier and its effect on the cell monolayer integrity. The differences between the viability of cells for M-MTX and Sol-MTX were significantly different when applied to ANOVA according to 2 x 8 factorial randomized design (p:0.016; for alpha: 0.05, power : 0.695). According to the in vitro cytotoxicity studies, we concluded that when MTX was incorporated into the microemulsion (M-MTX), which is a new drug carrier system, it suppresses tumour cell growth on multiple tumor lines. These results indicate that M-MTX may exert a low cytotoxic effect on normal cells and may be effective as an antitumor agent that induces apoptosis.