ИСТИНА

Selective delivery of drugs and diagnostic agents in the body is the focus of many research groups in the world. One of the promising nanocontainers is nanogel – soft nanoparticles, consisting of hydrophilic or amphiphilic polymeric chains. Nanogels have beneficial characteristics: high loading capacity, stability and sensitivity to environmental changes (pH, ionic strength and temperature). The aim of this study was to synthesize the nanogels and to analyze the loading and release kinetic of anticancer drug Dioxadet. Nanogels were synthesized from block-copolymer polyethylene glycol-b-polymethacrilic acid (PEG-b-PMAA). Synthesis consists of several steps: 1) formation of polymer polyelectrolyte complexes with oposetly charged ions (e.g. Ca2+); 2) cross-linking of formed nanoparticles by ethylenediamine using carbodiimide; 3) removing Са2+ ions from nanoparticles through chelating with EDTA and thorough dialysis. Loading of drug into nanogels was processed by their mixing at different molar ratios and pH (25ºС, 10h). Loaded nanogels were purified by multiple centrifugation on Amicon filters (MWCO 30 kDa). Loading capacity was calculated with help of spectrophotometric analysis. Release of drug was studied at different pH and temperature. Stable negatevly charged nanogels with cross-linked core were synthesized and characterized. Using DLS method we found that size and ζ-potential of nanogel changed during drug loading. Loading capacity of nanogels was strongly dependent on the ambient pH during the process (max loading capacity was at pH7 – 45%). We found the optimal pH and molar ratio drug/nanogel, wchich led to stable drug-loaded nanoparticles. The release of drugs was slow and slightly depended on pH as analyzed by dialysis method. Finally, the synthesized particles can be loaded with highly potent drug Dioxadet and exhibit sustained release of drug.