Self-assembled drug delivery systems. Part 6: in vitro/in vivo studies of anticancer N-octadecanoyl gemcitabine nanoassemblies.

The nanoassemblies were prepared from N-octadecanoyl gemcitabine (NOG)/cholesteryl succinyl poly(ethylene glycol) 1500 (CHS-PEG(1500)) (5:1, mol/mol). They showed higher cytotoxicity than gemcitabine on HpG2 cell model. The amphiphilicity of NOG may improve permeation of prodrugs and destruction of cell membrane. The nanoassemblies were rapidly eliminated from circulation after bolus intravenous administration to healthy and tumor-bearing mice. The in vivo distribution sites of NOG were mainly liver and spleen though the distribution in tumor was not high. The non-spherical shape and high surface charge of the nanoassemblies may affect distribution. The nanoassemblies had similar anticancer efficacy to free gemcitabine solutions when the former contained about 1/3 dose of the latter in gemcitabine form. The nanoassemblies would be a promising anticancer nanomedicine.