title: Anti-tumor activity of carmofur water-solubilized by lactic acid oligomer-grafted pullulan nanogels.
abstract: 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.
authors.affiliation: Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Miyazaki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D005936:Glucans / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D049329:Nanostructures; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D005936:Glucans; D019344:Lactic Acid; C009109:pullulan; C017367:carmofur; D005472:Fluorouracil; D004121:Dimethyl Sulfoxide