Antibodies Processed Using High Dilution Technology Distantly Change Structural Properties of IFNγ Aqueous Solution

Abstract

Terahertz spectroscopy allows for the analysis of vibrations corresponding to the large-scale structural movements and collective dynamics of hydrogen-bonded water molecules. Previously, differences had been detected in the emission spectra of interferon-gamma (IFNγ) solutions surrounded by extremely diluted solutions of either IFNγ or antibodies to IFNγ without direct contact compared to a control. Here we aimed to analyse the structural properties of water in a sample of an aqueous solution of IFNγ via terahertz time-domain spectroscopy (THz-TDS). Tubes with the IFNγ solution were immersed in fluidised lactose saturated with test samples (dilutions of antibodies to IFNγ or control) and incubated at 37 °C for 1, 1.5-2, 2.5-3, or 3.5-4 h. Fluidised lactose was chosen since it is an excipient in the manufacture of drugs based on diluted antibodies to IFNγ. After incubation, spectra were recorded within a wavenumber range of 10 to 110 cm^-1 with a resolution of 4 cm^-1. Lactose saturated with dilutions of antibodies to IFNγ (incubated for more than 2.5 h) changed the structural properties of an IFNγ aqueous solution without direct contact compared to the control. Terahertz spectra revealed stronger intermolecular hydrogen bonds and an increase in the relaxation time of free and weakly bound water molecules. The methodology developed on the basis of THz-TDS could potentially be applied to quality control of pharmaceuticals based on extremely diluted antibodies.

Keywords: high dilutions; interferon-gamma; lactose; new properties; structural properties; terahertz; water hydrogen bonds.

Figure 1

Dielectric permittivities (real $$\epsilon \prime$$ and imaginary $$\epsilon ″$$ parts) of the aqueous phase of the studied IFNγ solutions. The total incubation times of IFNγ solutions in the saturated lactose (black line ($$\epsilon \prime$$) or dashes ($$\epsilon ″$$)) and control (gray ($$\epsilon \prime$$) or dashes ($$\epsilon ″$$)) environment are 1 h (a), 1.5–2 h (b), 2.5–3 h (c), 3.5–4 h (d).