Comparison of Different Crosslinking Methods for Preparation of Docetaxel-loaded Albumin Nanoparticles

In the last step of desolvation method for preparation of albumin nanoparticles, glutaraldehyde (GA) is added to stabilize the newly formed nanoparticles. Due to undesirable effects of GA, the objective of this study was to evaluate alternative methods of crosslinking including ultraviolet (UV) irradiation, adding of glucose and combination of both methods. The nanoparticles were prepared by desolvation procedure. Final particle size, zeta potential, FTIR, scanning electron micrograph, cellular uptake and cell toxicity of nanoparticles crosslinked with UV and/or glucose were compared with commonly crosslinked nanoparticles with GA. Moreover, drug release and stability parameters of docetaxel-loaded albumin nanoparticles were investigated. Size of all nanoparticles prepared by different methods was in the same range (100-200 nm). Zeta potential showed the same results except for those treated with UV. The results of FTIR assay were the same for all groups. Although crosslinking by UV or glucose alone resulted in cytotoxic effects, combination of UV and glucose had less cytotoxic effects compared to GA. Cellular uptake of nanoparticles crosslinked with UV + glucose and GA showed similar results. The release of docetaxel from UV + glucose and GA crosslinked nanoparticles showed the same biphasic release. These data support the idea that crosslinking with a combination of UV and glucose can be a promising alternative method for production of docetaxel-loaded albumin nanoparticles with the advantage of omitting toxic GA.