Encapsulation of gemcitabine lipophilic derivatives into polycyanoacrylate nanospheres and nanocapsules

The aim of this study was to develop both a physical and a chemical protection of the anticancer drug gemcitabine, which suffers from a rapid plasmatic metabolization. For this purpose, we used a series of lipophilic derivatives of gemcitabine in which an acyl chain is covalently coupled to the 4-amino group of gemcitabine; moreover, a physical protection of the drug was attempted by incorporating these lipophilic derivatives into poly(H2NPEGCA-co-HDCA) nanospheres and nanocapsules. Nanoparticles were prepared by nanoprecipitation of the poly(H2NPEGCA-co-HDCA) copolymer and their size, zeta potential and encapsulation efficiency were further characterized. These results have been relied on lipophilicity and flexibility studies. Data showed that only the more lipophilic derivative, 4-(N)-stearoylgemcitabine, was incorporated with a high yield. Thus, 4-(N)-stearoylgemcitabine-containing nanospheres and nanocapsules were further analyzed by differential scanning calorimetry. Their cytotoxicity was tested on two human cancer cell lines and compared to that of gemcitabine and free 4-(N)-stearoylgemcitabine.