Application of solid-phase ion exchange method for saturation nanoionites with drugs in the absence of a background electrolyte

Abstract

The problem of developing systems for targeted drug delivery using nanosized carriers is currently an urgent issue. Therefore, polymeric materials due to their physical properties, high drug transfer capacity, bio-compatibility, and low toxicity are of great interest. Nanosized ion exchangers (NIEX) obtained in the form of stable hydrosols (cationic - NIC and anionic - NIA) based on their characteristics have the potential to be used as carriers of ionic forms of drugs.
The aim of this study was the description of the method for obtaining pure dosage forms based on nanoionites by the solid phase ion exchange method, which is possible only if one phase is a macroionite, and the other is a nanoionite of the same polarity.
The method is illustrated by the example of obtaining NIA in the form of an anion of di-N-methylglu-camine salt of gadopentate (trade name "Magnevist") – a contrast agent for MRI. The production of targeted drug delivery is important due to the potential toxicity of gadolinium compounds.
An independent study of solid-phase ion exchange for systems with macroionites was carried out. The experiment consisted in the transfer of a certain ion from one anion exchange column (1) in (Br-) form to another, the same, but in OH-form (2), by passing the NIA nanosized hydrosol of known concentration through a system of columns connected in series. The degree of transfer of bromide was controlled by measuring the concentration of Br- washed from the column 2 by sodium alkali solution after separation of the columns. Bromide was determined chromatographically. We determined that the solid-phase ion exchange was complete by balancing the amount of equivalents of the passed NIA and washed bromide. Bromide was completely transferred from column 1 to column 2.
After proving the efficiency of the solid-phase ion exchange method, we applied this approach for the production of particles of NIA nanosized hydrosol loaded with the [Gd-DTPA]^2- anion. We used macroanionite and NIA in salt forms, since the gadolinium complex is stable in neutral and weakly acidic media. Control of the completeness of the transfer of AV-17 (Сl-) into the [Gd-DTPA]^2– form was carried out by the simultaneous ion chromatographic determination of both anions in the samples taken at the column outlet. Next, the gado-linium complex was transferred to nanosized hydrosol (Br-), passing the NIA through the column with macroanionite in the form [Gd-DTPA]^2-. Thus, in the process of solid-phase ion exchange, the NIA hydrosol was saturated with the [Gd-DTPA]^2-, displacing bromide into the macroanionite phase.
Hydrosol obtained by solid-phase ion exchange in the form of [Gd-DTPA]^2- was submitted for testing at the Pirogov Russian National Research Medical University.
Due to the possibilities of solid-phase ion exchange, nanoionites can be easily and quickly converted into the ionic form of a drug, polystyrene nanoparticles can be saturated without losing expensive components in the surrounding solution. The absence of extraneous chemical impurities in the resulting preparation is of primary importance for its medical use, as this minimizes unwanted side effects.