New approaches to quality control of drugs from the group of branched polymers on the example of dextran

Relevance. Colloidal blood substitutes — polyglukins — have been used in infusion therapy for 70 years and are widely represented in modern pharmaceutical regulatory documentation. Glucose polymer with a(1→6) glycosidic linkages (dextran), as the main active pharmaceutical ingredient of polyglukins, has exceptional properties, such as long-term circulation in the bloodstream, inertness, volemic, detoxification, and antithrombotic effects. Quality authentication control of polyglukins usually includes FT-IR spectroscopy, while systems of polymeric micelles require characterization of dispersion and the electrophoretic properties that are in unambiguous correspondence with their biological activity. The aim of the study was to develop new approaches based on laser scattering methods to identify polymer-­based blood substitute drugs to complement existing regulatory documentation, and assess their biological activity using the Spirotox method. Materials and Methods. Reopolyglukin (Rpg) — an aqueous solution of dextran with amolecular weight of 30—40 kDa (Dex35) and 0.9% sodium chloride; water with different contents of the heavy isotope , Malvern Zetasizer ZSP equipment for measuring hydrodynamic radius (d, nm), zeta potential of colloids (ξ, mV); Biotesting method with Spiostomum ambigia cell for evaluating survival time in different dilutions of Rpg. Results and Discussion. Determination of submicron dispersity in the initial Rpg and in dilutions of water isotopologues indicates the presence of particles d50(Median) = 10 nm with avolume concentration V = 18% and alow polydispersity index PDI ~ 0.2. It is shown that the size distribution of nanoparticles is influenced by anoticeable effect is the concentration of the isotope. Biopharmaceutical analysis with the usage of Protozoa based on the Arrhenius kinetic model showed adecrease in the toxicity of aqueous solutions of Rpg in an environment with areduced content of the isotope . New approaches based on the use of laser analysis methods have been developed to characterize the dispersion properties and colloidal stability of polymer-­based blood substitutes. Conclusion. The results obtained can be included into the new edition of apharmacopeial article on Reopolyglukin preparations.