Betulin and its esters are the natural compounds with high in vitro cytotoxicity toward many cancer cells. However, the poor water solubility of these compounds has limited their applications. We prepared new composites of betulin esters using two methods, namely ball-milling of the mixtures of betulin esters with arabinogalactan and preparation of thin films of these mixtures by evaporating the aqueous solutions. These composites revealed higher water solubility as compared with the initial substances without losing the structural integrity and functionality. As a result, the new composites have shown much higher inhibitory effects against different cancer cell lines such as Ehrlich ascites carcinoma cells and lung carcinoma cells (A549) in comparison with the initial substances. The cell viability studies based on Annexin V and Propidium iodide probes have confirmed the high proapoptotic effect of betulin ester derivatives against cancer cells. Graphical abstract

The nanocomposites of piroxicam and indomethacin with fine porous inorganic oxides, alumina, silica, and magnesia, were obtained by high energy ball milling. Except for the piroxicam–alumina system, the composites revealed higher dissolution rate and solubility of the drugs as compared to the initial ones. The changes in the IR spectra suggested the interaction of the components during ball milling. It was assumed that the formation of new bonds at the contacts of particles in the composite resulted in stabilization of drugs in a metastable state inhibiting their transition into the initial crystalline form.