Characterization of G4 PAMAM dendrimer complexes with 5-fluorouracil and their interactions with bovine serum albumin

摘要

The success of novel therapeutic strategies relies strongly on the development of a reliable active agent delivery mechanism. In this work, we address the question of how G4 PAMAM dendrimers form complexes with a therapeutic agent, 5-fluorouracil (5-FU) and interact with bovine serum albumin (BSA). The analytical techniques, such as: UV-vis spectrophotometry, dynamic light scattering, electrophoretic mobility, Fourier-transform infrared spectroscopy (FTIR), multi-parametric surface plasmon resonance (MP-SPR) and quartz crystal microbalance with dissipation monitoring (QCM-D) were used to analyze the properties of the created complexes. Through running these experiments, the optimum conditions for drug-dendrimer complexation could be determined. The results show that similar to 70% of the 5-FU was loaded onto the G4 PAMAM dendrimers with higher capacity at pH 7.4 in comparison to acidic conditions. Biomolecule interactions with dendrimer carriers are driven both by electrostatic and hydrophobic forces. Dendrimer surface charge is reduced upon contact with protein and changes from 61 mV to 16.9 mV. This new understanding of dendrimers as nanocarriers and their interactions with plasma proteins delivers new insight into the interaction mechanism when the nanoparticles enter physiological fluids.