Self-assembly of N-acyl derivatives of gemcitabine at the air/water interface and the formation of nanoscale structures in water

Molecular self-assembly of nucleosides is important, and the resulting nanostructures may be used in drug delivery. Gemcitabine, a nucleoside anticancer agent, was conjugated with long-chained fatty acids to obtain two amphiphilic derivatives, N-octadecanoyl gemcitabine (NOG) and N-dodecanoyl gemcitabine (NDG). NDG formed a more flexible monolayer at the air/water interface than NOG. The mixed monolayers of cholesteryl succinyl poly(ethylene glycol)1500 (CHS-PEG1500) and NOG exhibited miscibility and an increase in flexibility. NDG formed unstable nanofibers in water. NOG produced nanoscale vesicles, and nanotubes were formed after removing the solvent. The NOG/CHS-PEG1500 mixture formed nanoscale assemblies of various morphologies depending on their molar ratios, solvent, processing methods and concentration. Worm-like micelles containing predominantly CHS-PEG1500 and rice-like vesicles containing predominantly NOG were simultaneously formed, and spherical micelles were obtained after removing the solvent. Unique leaf-like assemblies were produced after the concentration was increased. The assemblies have the potential to be a promising drug delivery system.