A. L. Nikolaev

Use of solid-phase inhomogeneities to increase the efficiency of ultrasonic therapy of oncological diseases

Authors’ concepts on the use of solid-phase sonosensitizer nanoinclusions in biological structures as ultrasonic energy concentrators in the therapy of oncological diseases are developed. The possibility of directed synthesis of nanoparticles and their aggregates in tumor tissue depending on its growth features is discussed. It was found that acoustic effects in polymer structures containing solid-phase inclusions depend on the nature of these inclusions and their bond with the polymer matrix. Using model gel systems, it was shown that solid-phase sonosensitizers enhance local thermal effects and amplitude-dependent scattering of ultrasound during its propagation in gel. Experimental studies on animals showed that the ultrasound exposure of malignant tumors containing nanoparticles of gold and some complex compounds results in a significant therapeutic effect.

Localization of acoustic energy in gel systems on solid-phase inhomogeneities

The thermal effects of ultrasound on an agarose gel containing nanoparticles of iron(III) hydroxide and barium sulfate are comparatively studied. The agarose matrix is shown to interact differently with iron(III) hydroxide and barium sulfate. The relative change in ultrasound absorption due to modifier particles located in the gel is estimated. The highest thermal effect is observed for systems in which modifiers are located on separate elements of the matrix bulk. Production of “containers” with ultrasound-controlled drug release on the basis of thermosensitive gels containing solid-phase inclusions is discussed as an example of possible application of the effects described.

Combined method of ultrasound therapy of oncological diseases

The experience of the joint research by the Department of Chemistry, Lomonosov Moscow State University, and the Federal State Budgetary Scientific Institution “N.N. Blokhin Russian Cancer Research Center” (FSBSI “N.N. Blokhin RCRC”), on the application of medium-intensity ultrasound in combination with chemotherapy and sonosensitizers in the treatment of cancer diseases was summarized. A cycle of preclinical trials showed that the method allows enhancing the damaging effect of ultrasound on the tumor, while no metastasis-promoting and toxic effects are exerted. The combined method is being currently tested in clinical trials.

Mechanism of crystal modification of ferrihydrite by polymer hydrogels according to data of Mössbauer spectroscopy

The effect of a polymer hydrogel matrix and an ultrasonic field on the formation of a phase of iron(III) hydroxide is studied by means of Mössbauer spectroscopy. Polyacryl amide (PAA) and gelatin are chosen as polymer matrices for hydrogels. The transformation of iron hydroxide is interpreted as the formation of ferrihydrite with two different forms of iron relative to imperfect and relatively perfect fragments of the structure of crystallites. It is shown that the ultrasonic field and (in some cases) the polymer matrix have a substantial effect on the processes of crystallization of the dispersed phase.

Thermoresponsive hydrogels with ultrasound-controlled properties

Possibility of creation of materials with transport properties operated by ultrasound on the basis of thermosensitive hydrogels modified by a solid phase of inorganic compounds is shown. The kinetic model of drug release from the hydrogel matrix, which allows to optimize the parameters of ultrasound exposure is proposed. Various options of devices with operated ultrasound an outlet of medicinal substance are offered.

A hierarchical model of crystallization in polymeric gels and porous solids

A kinetic model of the crystallization of substances in the volume of an agglomerate of many microparticles or in a polymeric gel in solution with a given composition and temperature was formulated. The model takes into account the diffusion of the crystallizing substance from outside into the space between microparticles in an agglomerate or between polymeric globules in a gel and then from this space into the volume of microparticles (globules) with the simultaneous nucleation and growth of microcrystals of the crystallizing substance. The possibility of simultaneous diffusion of several crystallizing substances, which chemically react with each other to produce product microcrystals, heating of the gel (solid) by the heat of crystallization, pushing the solution out from the space between microparticles, and changes in the volume of the gel (solid) as a result of crystallization is considered. The model was used to develop a classification of crystallization types in gels and porous solids and interpret several phenomena described in the literature. A hypothesis was advanced concerning some unknown phenomena related to crystallization.

Stimulated aggregation in ensembles of microcrystals

Aggregates of calcium carbonate microcrystals precipitated from a highly supersaturated aqueous solution were found to form in two stages. At the first stage, high-porosity disordered aggregates (floccules), and at the second, low-porosity ordered aggregates (agglomerates) formed. The application of an acoustic field with a frequency of 2.64 MHz and radiation power 3 W/cm2 did not influence the kinetics of formation of microcrystals but accelerated aggregation by four orders of magnitude. This effect was explained by the sonostimulated desolvation of microcrystals colliding with the surface of aggregates and the corresponding decrease in the probability of the detachment from aggregates after collisions. The formation of microcrystals and aggregates in an acoustic field can be described by a Fokker-Planck-type equation. Taking this into account, a model of sonostimulated agglomeration revealing the direction of further investigations was formulated.