Abstract

Nano-carrier systems such as liposomes have promising biomedical applications. Nevertheless, characterization of these complex samples is a challenging analytical task. In this study a coupled hydrodynamic chromatography-single particle-inductively coupled plasma mass spectrometry (HDC-spICP-MS) approach was validated based on the technical specification (TS) 19590:2017 of the international organization for standardization (ISO). The TS has been adapted to the hyphenated setup. The quality criteria (QC), e.g., linearity of the calibration, transport efficiency, were investigated. Furthermore, a cross calibration of the particle size was performed with values from dynamic light scattering (DLS) and transmission electron microscopy (TEM). Due to an additional Y-piece, an online-calibration routine was implemented. This approach allows the calibration of the ICP-MS during the dead time of the chromatography run, to reduce the required time and enhance the robustness of the results. The optimized method was tested with different gold nanoparticle (Au-NP) mixtures to investigate the characterization properties of HDC separations for samples with increasing complexity. Additionally, the technique was successfully applied to simultaneously determine both the hydrodynamic radius and the Au-NP content in liposomes. With the established hyphenated setup, it was possible to distinguish between different subpopulations with various NP loads and different hydrodynamic diameters inside the liposome carriers.

Highlights

  • Nanoparticles (NPs) have unique physico-chemical properties which makes their application attractive in a broad range of industrial applications [1,2]

  • In this study the quality criteria (QC) of the technical specification (TS) of a conventional spICP-MS setup were compared with the results from a coupled hydrodynamic chromatography (HDC)-spICP-MS system

  • The application of a hyphenated separation technique based on spICP-MS can be time-consuming due to the separation technique-dependent dead time, the separation process and essential calibrations

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Summary

Introduction

Nanoparticles (NPs) have unique physico-chemical properties which makes their application attractive in a broad range of industrial applications [1,2]. The potential hazard of NPs depends on their intrinsic physico-chemical properties (composition, size, concentration and shape), their surface modifications and their interaction with the environment [5,6,7,8,9,10,11]. The latter results in the formation of a biocorona created by complex matrices (e.g., lipids in cosmetics, proteins in cell culture media or bio-fluids) and influence the uptake, dissolution or aggregation behavior of NPs in biological systems [12]. A QC based on these results for a hyphenated setup is the evaluation of a size mixture of at least 2 known particles

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