Synthesis and Investigation of the Physicochemical Properties of Mechanocomposites of Arabinogalactan with Cyclophosphamide

Abstract

To raise the efficacy and the selectivity of known medicinal substances (MS), methods have recently been developed to create systems for their directed transport in the body using various carriers. The problem of decreasing the toxicity and increasing the selectivity of antitumor MSs is particularly relevant. In recent years, studies are underway for the development of conjugates of MSs and the natural polymers, in particular, the non-starch polysaccharides, many of which manifest antitumor and immunomodulatory properties. Owing to the unique combination of physicochemical and biological properties, arabinogalactan from larch wood (AG) is one of the most promising tools for the development of complex preparations with elevated bioavailability and reduced toxicity. The aim of the present work is to obtain mechanocomposites of cyclophosphamide (CPA) with the initial arabinogalactan (molecular mass 16 645 Da) and its fragments (molecular mass 8380 Da) and to study their physicochemical properties. According to IR and ¹³С, ¹⁵N and ³¹Р NMR spectroscopy, long-term mechanochemical treatment does not lead to a change in chemical composition of CPA molecules, only the formation of hydrogen bonds NH···OH is observed. The data on X-ray analysis, IR and multinuclear NMR spectroscopy show that, with a weight ratio of 1 : 5 and 1 : 10, disordering of CPA crystallographic structure and its molecular dispersion without chemical interaction of the components occur in the matrix of the polysaccharide with mechanical treatment of mixtures of CPA–AG over 4–12 hours.