Aggregation stability of nanoparticles based on rare-earth elements in different microenvironment and biological media

Abstract

Background: Development of new pharmacological forms able to increase the therapeutic effectiveness of already known drugs, to reduce side effects, and to increase the comfort of treatment for the patient is an actual task of modern medicine and pharmacy. To solve the problem, one of the most promising directions in this field is the use of various nanomaterials, among which in recent years the main attention was drawn to nanomaterials based on rare earth elements (REEs). At the same time, the question of the relation between the biological activity of nanomaterials and their physical and chemical properties, as well as the features of interaction with microenvironments in biosystems, remain controversial. Objectives: Estimation of the aggregation stability of REE-based nanoparticles (NPs) in incubation media of different compositions and of the role of certain factors in stabilizing NPs in the biological microenvironment. Materials and methods: Aggregation stability of GdYVO4:Eu3+, LaVO4: Eu3+, CeO2, GdVO4:Eu3+ NPs was studied using dynamic and electrophoretic light scattering techniques. NPs were incubated in 5% glucose or buffers: 50 mM Tris buffer (with different pH within of physiological values); Igla МЕМ medium; Krebs-Ringer buffer pH 7.4; HBSS-buffer (HEPES-buffered saline-solution) pH 7.4, in the absence or presence of 0.2% BSA, for 30 minutes and 24 hours. The effect of oxidized and reduced glutathione on the stability of solutions of NPs in Tris buffer at various pH values was also determined. Results: The results have shown that in contrast to the stabilizing effect of 5% glucose solution significant aggregation of NPs is observed in saline systems. The highest degree of aggregation was observed in the Igla МЕМ and Krebs-Ringer buffer environment. Addition of 0.2% of albumin to all media prevented aggregation. Interaction of immunoglobulin with NPs leads to increase in hydrodynamic diameter, especially for some types of NPs, already at the smallest of the used protein concentrations. Oxidized but not recovered glutathione promoted aggregation of all types of orthovanadate NPs in acidic medium (Tris buffer pH=6.7). Conclusions: The aggregative stability of NPs in the salt media increases significantly in the presence of serum albumin due to changes in the ratio of the electrostatic and steric components of the interaction of NPs with the microenvironment.