Evaluation of nanoparticles (NPs) for biomedical applications has received a lot of attention for detailed study on pharmacokinetics prior to clinical application. In this study, pure C-SiO₂ (crystalline silica) NPs and SiO₂ nanocomposites with silver (Ag) and zinc oxide (ZnO) were prepared by utilizing different synthesis routes such as sol-gel and co-precipitation techniques. The prepared NPs showed highly crystalline nature as confirmed by X-ray diffraction analysis where average crystallite sizes of 35, 16, and 57 nm for C-SiO₂, Ag-SiO₂, and ZnO-SiO₂ NPs, respectively, were calculated. Fourier transform infrared analysis confirmed the presence of functional groups related to the chemicals and procedures used for sample preparation. Due to agglomeration of the prepared NPs, the scanning electron microscope images showed large particle sizes when compared to their crystalline sizes. The optical properties of the prepared NPs such as absorption were obtained with UV-Vis spectroscopy. For in vivo biological evaluation, albino rats, both male and female, kept in different groups were exposed to NPs with 500 μg/kg dose. Hematological, serum biochemistry, histo-architecture, oxidative stress biomarkers, and antioxidant parameters in liver tissues along with various biomarkers for the evaluation of erythrocytes were estimated. The results on hemato-biochemistry, histopathological ailments, and oxidative stress parameters exhibited 95% alteration in the liver and erythrocytes of C-SiO₂ NPs-treated rats while 75 and 60% alteration in the liver tissues of rats due to exposure to Ag-SiO₂ and ZnO-SiO₂ NPs, respectively, when compared with the albino rats of the control (untreated) group. Therefore, the current study showed that the prepared NPs had adverse effects on the liver and erythrocytes causing hepatotoxicity in the albino rats in respective order C-SiO₂ > Ag SiO₂ > ZnO-SiO₂. As the C-SiO₂ NPs appeared to be the most toxic, it has been concluded that coating SiO₂ on Ag and ZnO reduced their toxicological impact on albino rats. Consequently, it is suggested that Ag-SiO₂ and ZnO-SiO₂ NPs are more biocompatible than C-SiO₂ NPs.

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