Anti-tumor activity of carmofur water-solubilized by lactic acid oligomer-grafted pullulan nanogels

Nanogels of pullulan grafted with L-lactic acid oligomer (LLA-o) were prepared to allow a lipophilic anti-tumor drug, carmofur, to solubilize in water. The number of LLA-o grafted was increased with an increase in the amount of LLA-o added in preparation. The LLA-o-grafted pullulan showed critical aggregation concentrations and had 20-100 nm in diameter depending on the grafted number. The carmofur was water-solubilized by the LLA-o-grafted pullulan self-assemble (nanogel), and inhibited the in vitro growth of tumor cells to a similar or high extent compared with carmofur solution in dimethyl sulfoxide (DMSO). When incubated with the spheroid of tumor cells, the nanogel with carmofur showed a strong suppressive effect of tumor cells grown, in contrast to the carmofur solution. When intratumorally injected into mice carrying a tumor mass, carmofur water-solubilized by the nanogel showed stronger suppressive effect of tumor cells growth. It is concluded that the nanogel is a promising carrier to water-solubilize carmofur and enhance the in vitro and in vivo anti-tumor effects.