Gemcitabine (
Gemzar(®)) is the first line treatment for
pancreatic cancer and often used in combination
therapy for non-small cell lung, ovarian, and metastatic breast
cancers. Although extremely toxic to a variety of
tumor cells in culture, the clinical outcome of
gemcitabine treatment still needs improvement. In the present study, a new
gemcitabine nanoparticle formulation was developed by incorporating a previously reported
stearic acid amide derivative of
gemcitabine into nanoparticles prepared from
lecithin/
glyceryl monostearate-in-water
emulsions. The stearoyl
gemcitabine nanoparticles were cytotoxic to
tumor cells in culture, although it took a longer time for the
gemcitabine in the nanoparticles to kill
tumor cells than for free
gemcitabine. In mice with pre-established model mouse or human
tumors, the stearoyl
gemcitabine nanoparticles were significantly more effective than free
gemcitabine in controlling the
tumor growth. PEGylation of the
gemcitabine nanoparticles with
polyethylene glycol (2000) prolonged the circulation of the nanoparticles in blood and increased the accumulation of the nanoparticles in
tumor tissues (>6-fold), but the PEGylated and un-PEGylated
gemcitabine nanoparticles showed similar anti-
tumor activity in mice. Nevertheless, the nanoparticle formulation was critical for the stearoyl
gemcitabine to show a strong anti-
tumor activity. It is concluded that for the
gemcitabine derivate-containing nanoparticles, cytotoxicity data in culture may not be used to predict their in vivo anti-
tumor activity, and this novel
gemcitabine nanoparticle formulation has the potential to improve the clinical outcome of
gemcitabine treatment.