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Background and purpose: In the last step of preparation of nanoparticles, glutaraldehyde (GA) is added to stabilize the formed nanoparticles. There are several reports indicating the harmful effects of glutaraldehyde on different organ systems and tissues. The aim of this study was to evaluate the effects of different cross-linking methods like using ultraviolet (UV) irradiation, glucose and combination of these methods on nanoparticles. Materials and methods: Nanoparticles were prepared by desolvation method and in the last step were cross-linked by four different methods. Nanoparticles were compared with each other based on properties like size, zeta potential [by Photon correlation spectroscopy (PCS)], Fourier transform infrared spectroscopy (FTIR), scanning electron micrograph, cellular uptake and toxicity. Results: All nanoparticles had the same range of size (100-200 nm) and only the zetapotential of UV treated group had significant difference with glutaraldehyde group. The results of scanning electron micrograph and FTIR assay were the same for all groups. Cross-linking by combination of UV and glucose had less toxic effects and more viable cells (76.59 ± 7.67 percent) compared to glutaraldehyde (40.08 ± 6.60 percent) (P < 0.01). Cellular uptake of nanoparticles cross-linked with UV and glucose and glutaraldehyde showed similar results. Conclusion: These findings support the idea that using combination of UV and glucose as cross-linking method can be an appropriate alternative method for toxic glutaraldehyde with less toxic effects.

Keywords: Nanoparticles, albumin, cross-linking, glutaraldehyde, ultraviolet, glucose

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