Svetlana L. Kotova

Development of novel formulations for photodynamic therapy on the basis of amphiphilic polymers and porphyrin photosensitizers. Porphyrin-polymer complexes in model photosensitized processes

We have studied the effect of amphiphilic polymers with different structure (polyvinylpyrrolidone, polyethyleneoxide and a triblock copolymer of ethylene- and propyleneoxide—(Pluronic F127)) on the photoactivity of a hematoporphyrin derivative (dimegin). It has been shown that such polymers can cause a considerable increase in the porphyrin photosensitizer (PPS) activity both in the process of singlet oxygen photogeneration and in the reaction of a substrate photooxidation in D2O and water. Among the studied polymers, polyvinylpyrrolidone appeared to have a most significant influence onto the photoactivity of dimegin. We attribute the observed effect of the amphiphilic polymers on the photoactivity of dimegin to the presence of polymer-porphyrin interactions resulting in the porphyrin disaggregation in aqueous phase. Using 1H NMR spectroscopy, we have found that dimegin binds to the polymers via the PPS interaction mainly with the hydrophobic fragments of polymeric macromolecules. However, in the case of polyvinylpyrrolidone we observed also PPS interactions with the hydrophilic fragments of macromolecules.

Specific Features of Early Stage of the Wound Healing Process Occurring Against the Background of Photodynamic Therapy Using Fotoditazin Photosensitizer–Amphiphilic Polymer Complexes

There is a growing demand on the studies of the wound healing potentials of photodynamic therapy. Here we analyze the effects of Fotoditazin, an e6 chlorine derivative, and its complexes with amphiphilic polymers, on the early stage of wound healing in a rat model. A skin excision wound model with prevented contraction was developed in male albino rats divided into eight groups according to the treatment mode. All animals received injections of one of the studied compositions into their wound beds and underwent low‐intensity laser irradiation or stayed un‐irradiated. The clinical monitoring and histological examination of the wounds were performed. It has been found that all the Fotoditazin formulations have significant effects on the early stage of wound healing. The superposition of the inflammation and regeneration was the main difference between groups. The aqueous solution of Fotoditazin alone induced a significant capillary hemorrhage, while its combinations with amphiphilic polymers did not. The best clinical and morphological results were obtained for the Fotoditazin–Pluronic F127 composition. Compositions of Fotoditazin and amphiphilic polymers, especially Pluronic F127, probably, have a great potential for therapy of wounds. Their effects can be attributed to the increased regeneration and suppressed reactions changes at the early stages of repair.

Quantitative evaluation of atherosclerotic plaques using cross-polarization optical coherence tomography, nonlinear, and atomic force microscopy

Abstract. A combination of approaches to the image analysis in cross-polarization optical coherence tomography (CP OCT) and high-resolution imaging by nonlinear microscopy and atomic force microscopy (AFM) at the different stages of atherosclerotic plaque development is studied. This combination allowed us to qualitatively and quantitatively assess the disorganization of collagen in the atherosclerotic arterial tissue (reduction and increase of CP backscatter), at the fiber (change of the geometric distribution of fibers in the second-harmonic generation microscopy images) and fibrillar (violation of packing and different nature of a basket-weave network of fibrils in the AFM images) organization levels. The calculated CP channel-related parameters are shown to have a statistically significant difference between stable and unstable (also called vulnerable) plaques, and hence, CP OCT could be a potentially powerful, minimally invasive method for vulnerable plaques detection.

Photocatalytic activity of water-soluble tetrapyrrole compounds in the presence of amino-containing polymers

It was demonstrated that the activity of tetrapyrrole photosensitizers (TPSs) of singlet oxygen generation (dimegin, tetrasulfophenylporphyrin, and photoditasine) in the oxidation of tryptophan in the aqueous phase decreases in the presence of polymers containing free amino groups (chitosan and polyallylamine). The decrease of the activity is accompanied by the change of the electronic absorption spectra of the TPSs. Analogues of chitosan with screened amino groups (chitosan sulfate and carboxymethylchitin) or without amino groups (carboxymethylcellulose), as well as hexamethylenediamine, a low-molecular-weight compound, do not affect the activity of the TPSs. The regularities observed can be accounted for by the association of molecules of the tetrapyrroles initiated by the complexation of the TPSs having external salt groupings with free amino groups of the polymers.

Atomic Force Microscopy Study of Atherosclerosis Progression in Arterial Walls.

Cardiovascular disease remains the leading cause of mortality worldwide. Here we suggest a novel approach for tracking atherosclerosis progression based on the use of atomic force microscopy (AFM). Using AFM, we studied cross-sections of coronary arteries with the following types of lesions: Type II-thickened intima; Type III-thickened intima with a lipid streak; Type IV-fibrotic layer over a lipid core; Type Va-unstable fibrotic layer over a lipid core; Type Vc-very thick fibrotic layer. AFM imaging revealed that the fibrotic layer of an atherosclerotic plaque is represented by a basket-weave network of collagen fibers and a subscale network of fibrils that become looser with atherosclerosis progression. In an unstable plaque (Type Va), packing of the collagen fibers and fibrils becomes even less uniform than that at the previous stages, while a stable fibrotic plaque (Vc) has significantly tighter packing. Such alterations of the collagen network morphology apparently, led to deterioration of the Type Va plaque mechanical properties, that, in turn, resulted in its instability and propensity to rupture. Thus, AFM may serve as a useful tool for tracking atherosclerosis progression in the arterial wall tissue.

Chitosan impregnation with biologically active tryaryl imidazoles in supercritical carbon dioxide

The presented paper is focused on impregnation of chitosan and its derivatives with a biologically active triaryl imidazole model compound ((2-2-hydroxyphenyl)-4.5-diphenyl-1H-imidazole) in the supercritical carbon dioxide medium. Since initial chitosan represents a polycation-exchange resin and does not swell in supercritical carbon dioxide, the impregnation was carried out in the presence of water (0.15–3.0 vol%). The maximum 2-2-hydroxyphenyl)-4.5-diphenyl-1H-imidazole concentration in a chitosan film was achieved at the ~5 × 10−3 g/cm3 water content in the reactor. We also used hydroxy carboxylic acid derivatives of chitosan and its copolymer with polylactide as matrices for introduction of hydrophobic 2-2-hydroxyphenyl)-4.5-diphenyl-1H-imidazole. We have shown that unmodified chitosan contains the greatest amount of 2-2-hydroxyphenyl)-4.5-diphenyl-1H-imidazole, as compared with its hydrophobic derivatives. The kinetics of 2-2-hydroxyphenyl)-4.5-diphenyl-1H-imidazole diffusion from a chitosan matrix was studied in acidified water with pH 1.6. We found that the complete release of 2-2-hydroxyphenyl)-4.5-diphenyl-1H-imidazole into the aqueous phase from unmodified chitosan films occurred in 48 h, while its complete release from chitosan modified with hydroxy carboxylic acids occurred in 5 min or less.

Optimization of Photosensitized Tryptophan Oxidation in the Presence of Dimegin-Polyvinylpyrrolidone-Chitosan Systems

By the example of a model process of tryptophan photooxidation in the aqueous medium in the presence of a three-component photosensitizing complex (porphyrin photosensitizer-polyvinylpyrrolidone- chitosan, PPS-PVP-CT) in the temperature range of 20–40 °С, we have demonstrated a possibility of modification of such a process by selecting different molar ratios of the components in the reaction mixture. The actual objective of this selection is the formation of a certain PPS-PVP-CT composition in which PVP macromolecules would coordinate with PPS molecules and at the same time practically block the complex binding of PPS molecules with chitosan macromolecules. Such blocking allows utilization of the bactericidal properties of chitosan to a greater extent, since chitosan is known to depress the PPS photosensitizing activity in PPS-PVP-CT complexes when using those in photodynamic therapy (PDT). The optimal composition of photosensitizing complexes appears to be dependent on the temperature at which the PDT sessions are performed. We have analyzed the correlations of the effective rate constants of tryptophan photooxidation with the photophysical characteristics of the formed complexes.

AFM of tissue sections is a useful complementary tool as a biomedical marker

Abstract The aim of the study was to demonstrate a good diagnostic potential of atomic force microscopy (AFM) in tracking morphological changes in the extracellular matrix (ECM) of connective tissue due to pathological processes. Here we summarize our experience in AFM application in a number of biomedical studies on the connective tissue disease, both for research and clinical purposes. AFM has been shown to reveal visible deviations from the normal morphology of the extracellular matrix in diseased tissues. We found that AFM and related techniques are capable of tracking disease-related changes at different levels of collagen organization in the ECM. AFM may also monitor a ratio between collagen and non-fibrous material of the ECM, for example, in inflammatory and neoplastic processes. The FNS parameters provide quantification of the morphological changes visualized by AFM. The PeakForce QNM and nanoindentation studies give a further insight into the state of ECM via tracking changes in the local mechanical and adhesive properties. All our AFM studies appeared in a good agreement with the histological findings and generally had a superior sensitivity to the ECM pathological changes. AFM may serve as a valuable complementary diagnostic tool for tracking pathological changes in the connective tissue.

Mesenchymal Stem Cell Therapy For Ischemic Heart Disease: Advances And Challenges

Ischemic Heart Disease (IHD) has been recognized as the main cause of mortality in the modern world. Application of cell therapy technologies for the IHD treatment has been actively studied from the beginning of 2000s. The review is dedicated to the use of mesenchymal stem cells (MSC) in the therapy of IHD. The strategies of the MSC modification in vitro for improvement of their regenerative potential are extensively discussed, including preconditioning to enhance the cell survival, boosting their paracrine effect and manipulating their cardiomyogenic differentiation. The optimization of the MSC delivery and opportunities related to the use of biomaterials as cell carriers are also discussed. The results of the most important clinical studies on the MSC-based IHD therapy are presented, including those completed and published in the literature and the ongoing clinical trials registered at clinicaltrials.gov by June 2018.

Photocatalytic Properties of Tetraphenylporphyrins Immobilized on Calcium Alginate Aerogels

We have prepared photocatalytic systems based on tetraphenylporphyrins (TPP) immobilized on calcium alginate solid gels in the conditions of thermal drying on air (xerogel), freeze drying in vacuum (cryogel) and supercritical drying in the supercritical carbon dioxide (scCO2) medium (aerogel). As a test reaction to measure the prepared systems’ efficiency, we studied tryptophan photooxidation in the aqueous medium. We have demonstrated that the systems with aerogel as a carrier exhibited the highest photocatalytic efficiency. In that case, the rate constant for the test substrate (tryptophan) oxidation exceeds the corresponding rate constants of similar systems based on xerogel and cryogel by more than 5 times. Moreover, the aerogel-based photocatalytic systems demonstrated enhanced functional stability and a possibility of multiple use of such a catalyst in tryptophan oxidation. Based on the data of small-angle X-ray scattering and thermooxidative destruction, we have made a conclusion about the relationship between the high photocatalytic activity of aerogel-immobilized TPP and formation of a developed porous aerogel structure in the conditions of drying in the scCO2 medium, which is stabilized due to formation of additional complex bonds of calcium ions with fragments of glycoside rings.