Olga Selyutina - Academia.edu (original) (raw)
Papers by Olga Selyutina
Membranes, 2022
The damage of cell membranes induced by photosensitive drugs has attracted the significant attent... more The damage of cell membranes induced by photosensitive drugs has attracted the significant attention of researchers in various fields of medicine. Ketoprofen (KP) is known to be the most photosensitive among the nonsteroidal anti-inflammatory drugs. The phototoxic side effects of KP and other non-steroidal anti-inflammatory drugs are associated with the action of free radicals, but there is insufficient information about the nature of these radicals. In the present study, free radicals formed upon KP irradiation within lipid membranes were studied using nuclear magnetic resonance (NMR) and chemically induced dynamic nuclear polarization (CIDNP) methods, as well as a molecular dynamics simulation. Our study confirmed the effective penetration of KP into the lipid bilayer and showed a significant effect of the nature of the medium on the photolysis mechanism. While, in a homogeneous solution, the main channel of KP photolysis is free radical-mediated monomolecular decomposition with f...
International Journal of Molecular Sciences, 2022
The antioxidant/pro-oxidant activity of drugs and dietary molecules and their role in the mainten... more The antioxidant/pro-oxidant activity of drugs and dietary molecules and their role in the maintenance of redox homeostasis, as well as the implications in health and different diseases, have not yet been fully evaluated. In particular, the redox activity and other interactions of drugs with essential redox metal ions, such as iron and copper, need further investigation. These metal ions are ubiquitous in human nutrition but also widely found in dietary supplements and appear to exert major effects on redox homeostasis in health, but also on many diseases of free radical pathology. In this context, the redox mechanistic insights of mainly three prototype groups of drugs, namely alpha-ketohydroxypyridines (alpha-hydroxypyridones), e.g., deferiprone, anthraquinones, e.g., doxorubicin and thiosemicarbazones, e.g., triapine and their metal complexes were examined; details of the mechanisms of their redox activity were reviewed, with emphasis on the biological implications and potential c...
Molecules, 2021
Deferasirox is an orally active, lipophilic iron chelating drug used on thousands of patients wor... more Deferasirox is an orally active, lipophilic iron chelating drug used on thousands of patients worldwide for the treatment of transfusional iron overload. The essential transition metals iron and copper are the primary catalysts of reactive oxygen species and oxidative damage in biological systems. The redox effects of deferasirox and its metal complexes with iron, copper and other metals are of pharmacological, toxicological, biological and physiological importance. Several molecular model systems of oxidative damage caused by iron and copper catalysis including the oxidation of ascorbic acid, the peroxidation of linoleic acid micelles and the oxidation of dihydropyridine have been investigated in the presence of deferasirox using UV-visible and NMR spectroscopy. Deferasirox has shown antioxidant activity in all three model systems, causing substantial reduction in the rate of oxidation and oxidative damage. Deferasirox showed the greatest antioxidant activity in the oxidation of as...
International Journal of Molecular Sciences, 2021
The peculiarities of spin effects in photoinduced electron transfer (ET) in diastereomers of dono... more The peculiarities of spin effects in photoinduced electron transfer (ET) in diastereomers of donor-acceptor dyads are considered in order to study the influence of chirality on reactivity. Thus, the spin selectivity—the difference between the enhancement coefficients of chemically induced dynamic nuclear polarization (CIDNP)—of the dyad’s diastereomers reflects the difference in the spin density distribution in its paramagnetic precursors that appears upon UV irradiation. In addition, the CIDNP coefficient itself has demonstrated a high sensitivity to the change of chiral centers: when one center is changed, the hyperpolarization of all polarized nuclei of the molecule is affected. The article analyzes the experimental values of spin selectivity based on CIDNP calculations and molecular dynamic modeling data in order to reveal the effect of optical configuration on the structure and reactivity of diastereomers. In this way, we succeeded in tracing the differences in dyads with L- an...
Molecules, 2021
Glycyrrhizic acid, or glycyrrhizin (GA), a major active component of licorice root, has been wide... more Glycyrrhizic acid, or glycyrrhizin (GA), a major active component of licorice root, has been widely used in traditional Chinese and Japanese medicine since ancient times. However, only in the last decades has a novel and unusual property of the GA been discovered to form water-soluble, supramolecular complexes with a variety of lipophilic drugs. These complexes show significant advantages over other known delivery systems, in particular, due to strong pH sensitivity, the properties of GA self-associates. In the present study, a supramolecular complex formation of the hypotensive and antiarrhythmic drug nifedipine with GA has been studied at different pH values, corresponding to the different degrees of GA dissociation, including a fully dissociated state of GA. Both NMR experiments and molecular dynamics simulations demonstrate the existence of the nifedipine complex with GA at all dissociation states of GA. However, optical absorption experiments show the decrease of complex stabil...
Current Drug Delivery, 2018
BACKGROUND Complexes of Genipin and different water-soluble adjuvant polysaccharides, such as ara... more BACKGROUND Complexes of Genipin and different water-soluble adjuvant polysaccharides, such as arabinogalactane, hydroxyethyl starch, fibergum, and oligosaccharides β-CD and HP-β-CD, were synthesized as drug delivery system using mechanochemical technology. METHOD We have investigated physicochemical properties, stability, and hepatotoxicity of the synthesized complexes in solid state and aqueous solution. The formation of the complexes was evidenced by different physical and spectroscopy assays, and the stability constants of our synthesized Genipin-based complexes were also calculated. RESULTS The HP-β-CD inclusion complex showed the highest characteristics. We have found that the molecule of Genipin was completely included in the cyclodextrin cavity of the HP-β-CD. This complex of Genipin has shown a 6.14-fold increase of solubility compared with the original Genipin, and more stable in solvent and solid states. CONCLUSION The hepatotoxicity assays showed that our investigated complexes of Genipin are much safer than the original Genipin. These results suggest that new Genipin-based preparations can be synthesized with advantageous of higher stability and safety.
Molecular Pharmaceutics, 2019
Praziquantel (PZQ) is one of the most widespread anthelmintic drugs. However, the frequent insuff... more Praziquantel (PZQ) is one of the most widespread anthelmintic drugs. However, the frequent insufficient application of PZQ after oral administration is associated with its low solubility, penetration rate, and bioavailability. In the present study, the permeation of PZQ through a 1,2-Page 1 of 41 ACS Paragon Plus Environment Molecular Pharmaceutics 2 dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane was investigated to probe glycyrrhizin assisted transport. Glycyrrhizin (or glycyrrhizic acid, GA), a natural saponin, shows the ability to enhance the therapeutic activity of various drugs when it is used as a drug delivery system. However, the molecular mechanism of this effect is still under debate. In the present study, the transport rate was measured experimentally by parallel artificial membrane permeation assay (PAMPA) and molecular dynamics (MD) simulation with DOPC lipid bilayers. The formation of the non-covalent supramolecular complex of PZQ with disodium salt of GA (Na2GA) in aqueous solution was proved by NMR relaxation technique. PAMPA experiments show a strong increase in the amount of the penetrating praziquantel molecules in comparison with a saturated aqueous solution of pure drug used as a control. MD simulation of PZQ penetration through the bilayer demonstrates an increase in permeability into the membrane in the presence of a glycyrrhizin molecule. A decrease in the free energy barrier in the middle of the lipid bilayer was obtained, associated with the hydrogen bond between PZQ and GA. Also, GA reduces the local bilayer surface resistance to penetration of PQZ by rearranging the surface lipid headgroups. This study clarifies the mechanism of increasing the drug's bioavailability in the presence of glycyrrhizin.
Journal of Drug Delivery Science and Technology, 2019
The aim of the study was to enhance the solubility and bioavailability of praziquantel (PZQ) thro... more The aim of the study was to enhance the solubility and bioavailability of praziquantel (PZQ) through mechanochemical preparation of its solid compositions with the disodium salt of glycyrrhizic acid (Na 2 GA). The compositions were studied in the solid phase by means of scanning electron microscopy, powder X-ray diffraction and thermal analysis, and in solutions by means of HPLC, gel permeation chromatography, phase solubility assay and 1 H NMR spectroscopy. PZQ permeability was studied by means of parallel artificial membrane permeability assay and with a monolayer of Caco-2 cells. The pharmacokinetic characteristics and acute toxicity of PZQ and its compositions were studied on mice. Solubility of PZQ in the compositions increases up to 3.5 times. The micelles in Na 2 GA solutions possess a molecular mass of ~60 kDa. An increase in PZQ solubility may be due to its inclusion into micelles of glycyrrhizic acid. The permeability of PZQ was found to be much higher from its composition with Na 2 GA in comparison with initial PZQ. An increase in PZQ bioavailability by a factor of 3 in laboratory mice and changes of pharmacokinetic curve shape were demonstrated for the oral administration of its composition with Na 2 GA. The solid compositions show high chemical stability under rapid storage test. The obtained PZQ compositions may be a promising basis for the development of anthelmintic preparations with increased efficiency.
Journal of Agricultural and Food Chemistry, 2017
To increase the bioavailability of plant protection products we have applied new approach based o... more To increase the bioavailability of plant protection products we have applied new approach based on non-covalent association with natural water soluble polysaccharides and oligosaccharides as delivery systems (DSs). The mechanochemical technique has been applied to prepare the solid state nano-dispersed compositions of antidote 1,8-naphthalic anhydride (NA) with arabinogalactan, sodium salt of carboxymethylcellulose, and glycyrrhizin as DSs. The effect of DSs on the solubility and the penetration of NA into the seeds of barley and wheat has been investigated by various physicochemical techniques. All DSs considerably enhance the solubility of NA and improve its penetration into the grain. The influence of polysaccharides and oligosaccharides on artificial lipid membrane was studied by NMR relaxation method. It was concluded, that the effect of polysaccharides and oligosaccharides on the penetration efficacy of plant protection products might be associated with the detected solubility enhancement and the affinity of DSs to the surface of cell membranes.
Russian Chemical Bulletin, 2017
Glycyrrhizic acid, arabinogalactan, and β cyclodextrin are capable of forming complexes with vari... more Glycyrrhizic acid, arabinogalactan, and β cyclodextrin are capable of forming complexes with various drug compounds significantly enhancing their solubility and bioavailability. To elucidate the mechanism of action of oligo and polysaccharides, the exchange time of transporting formate ions through the membrane of myeloblastic leukemia cells (K562) was measured by NMR spectroscopy with the addition of paramagnetic ions. It was found that glycyrrhizic acid and arabinogalactan substantially increased the membrane permeability.
Membranes, 2022
The damage of cell membranes induced by photosensitive drugs has attracted the significant attent... more The damage of cell membranes induced by photosensitive drugs has attracted the significant attention of researchers in various fields of medicine. Ketoprofen (KP) is known to be the most photosensitive among the nonsteroidal anti-inflammatory drugs. The phototoxic side effects of KP and other non-steroidal anti-inflammatory drugs are associated with the action of free radicals, but there is insufficient information about the nature of these radicals. In the present study, free radicals formed upon KP irradiation within lipid membranes were studied using nuclear magnetic resonance (NMR) and chemically induced dynamic nuclear polarization (CIDNP) methods, as well as a molecular dynamics simulation. Our study confirmed the effective penetration of KP into the lipid bilayer and showed a significant effect of the nature of the medium on the photolysis mechanism. While, in a homogeneous solution, the main channel of KP photolysis is free radical-mediated monomolecular decomposition with f...
International Journal of Molecular Sciences, 2022
The antioxidant/pro-oxidant activity of drugs and dietary molecules and their role in the mainten... more The antioxidant/pro-oxidant activity of drugs and dietary molecules and their role in the maintenance of redox homeostasis, as well as the implications in health and different diseases, have not yet been fully evaluated. In particular, the redox activity and other interactions of drugs with essential redox metal ions, such as iron and copper, need further investigation. These metal ions are ubiquitous in human nutrition but also widely found in dietary supplements and appear to exert major effects on redox homeostasis in health, but also on many diseases of free radical pathology. In this context, the redox mechanistic insights of mainly three prototype groups of drugs, namely alpha-ketohydroxypyridines (alpha-hydroxypyridones), e.g., deferiprone, anthraquinones, e.g., doxorubicin and thiosemicarbazones, e.g., triapine and their metal complexes were examined; details of the mechanisms of their redox activity were reviewed, with emphasis on the biological implications and potential c...
Molecules, 2021
Deferasirox is an orally active, lipophilic iron chelating drug used on thousands of patients wor... more Deferasirox is an orally active, lipophilic iron chelating drug used on thousands of patients worldwide for the treatment of transfusional iron overload. The essential transition metals iron and copper are the primary catalysts of reactive oxygen species and oxidative damage in biological systems. The redox effects of deferasirox and its metal complexes with iron, copper and other metals are of pharmacological, toxicological, biological and physiological importance. Several molecular model systems of oxidative damage caused by iron and copper catalysis including the oxidation of ascorbic acid, the peroxidation of linoleic acid micelles and the oxidation of dihydropyridine have been investigated in the presence of deferasirox using UV-visible and NMR spectroscopy. Deferasirox has shown antioxidant activity in all three model systems, causing substantial reduction in the rate of oxidation and oxidative damage. Deferasirox showed the greatest antioxidant activity in the oxidation of as...
International Journal of Molecular Sciences, 2021
The peculiarities of spin effects in photoinduced electron transfer (ET) in diastereomers of dono... more The peculiarities of spin effects in photoinduced electron transfer (ET) in diastereomers of donor-acceptor dyads are considered in order to study the influence of chirality on reactivity. Thus, the spin selectivity—the difference between the enhancement coefficients of chemically induced dynamic nuclear polarization (CIDNP)—of the dyad’s diastereomers reflects the difference in the spin density distribution in its paramagnetic precursors that appears upon UV irradiation. In addition, the CIDNP coefficient itself has demonstrated a high sensitivity to the change of chiral centers: when one center is changed, the hyperpolarization of all polarized nuclei of the molecule is affected. The article analyzes the experimental values of spin selectivity based on CIDNP calculations and molecular dynamic modeling data in order to reveal the effect of optical configuration on the structure and reactivity of diastereomers. In this way, we succeeded in tracing the differences in dyads with L- an...
Molecules, 2021
Glycyrrhizic acid, or glycyrrhizin (GA), a major active component of licorice root, has been wide... more Glycyrrhizic acid, or glycyrrhizin (GA), a major active component of licorice root, has been widely used in traditional Chinese and Japanese medicine since ancient times. However, only in the last decades has a novel and unusual property of the GA been discovered to form water-soluble, supramolecular complexes with a variety of lipophilic drugs. These complexes show significant advantages over other known delivery systems, in particular, due to strong pH sensitivity, the properties of GA self-associates. In the present study, a supramolecular complex formation of the hypotensive and antiarrhythmic drug nifedipine with GA has been studied at different pH values, corresponding to the different degrees of GA dissociation, including a fully dissociated state of GA. Both NMR experiments and molecular dynamics simulations demonstrate the existence of the nifedipine complex with GA at all dissociation states of GA. However, optical absorption experiments show the decrease of complex stabil...
Current Drug Delivery, 2018
BACKGROUND Complexes of Genipin and different water-soluble adjuvant polysaccharides, such as ara... more BACKGROUND Complexes of Genipin and different water-soluble adjuvant polysaccharides, such as arabinogalactane, hydroxyethyl starch, fibergum, and oligosaccharides β-CD and HP-β-CD, were synthesized as drug delivery system using mechanochemical technology. METHOD We have investigated physicochemical properties, stability, and hepatotoxicity of the synthesized complexes in solid state and aqueous solution. The formation of the complexes was evidenced by different physical and spectroscopy assays, and the stability constants of our synthesized Genipin-based complexes were also calculated. RESULTS The HP-β-CD inclusion complex showed the highest characteristics. We have found that the molecule of Genipin was completely included in the cyclodextrin cavity of the HP-β-CD. This complex of Genipin has shown a 6.14-fold increase of solubility compared with the original Genipin, and more stable in solvent and solid states. CONCLUSION The hepatotoxicity assays showed that our investigated complexes of Genipin are much safer than the original Genipin. These results suggest that new Genipin-based preparations can be synthesized with advantageous of higher stability and safety.
Molecular Pharmaceutics, 2019
Praziquantel (PZQ) is one of the most widespread anthelmintic drugs. However, the frequent insuff... more Praziquantel (PZQ) is one of the most widespread anthelmintic drugs. However, the frequent insufficient application of PZQ after oral administration is associated with its low solubility, penetration rate, and bioavailability. In the present study, the permeation of PZQ through a 1,2-Page 1 of 41 ACS Paragon Plus Environment Molecular Pharmaceutics 2 dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane was investigated to probe glycyrrhizin assisted transport. Glycyrrhizin (or glycyrrhizic acid, GA), a natural saponin, shows the ability to enhance the therapeutic activity of various drugs when it is used as a drug delivery system. However, the molecular mechanism of this effect is still under debate. In the present study, the transport rate was measured experimentally by parallel artificial membrane permeation assay (PAMPA) and molecular dynamics (MD) simulation with DOPC lipid bilayers. The formation of the non-covalent supramolecular complex of PZQ with disodium salt of GA (Na2GA) in aqueous solution was proved by NMR relaxation technique. PAMPA experiments show a strong increase in the amount of the penetrating praziquantel molecules in comparison with a saturated aqueous solution of pure drug used as a control. MD simulation of PZQ penetration through the bilayer demonstrates an increase in permeability into the membrane in the presence of a glycyrrhizin molecule. A decrease in the free energy barrier in the middle of the lipid bilayer was obtained, associated with the hydrogen bond between PZQ and GA. Also, GA reduces the local bilayer surface resistance to penetration of PQZ by rearranging the surface lipid headgroups. This study clarifies the mechanism of increasing the drug's bioavailability in the presence of glycyrrhizin.
Journal of Drug Delivery Science and Technology, 2019
The aim of the study was to enhance the solubility and bioavailability of praziquantel (PZQ) thro... more The aim of the study was to enhance the solubility and bioavailability of praziquantel (PZQ) through mechanochemical preparation of its solid compositions with the disodium salt of glycyrrhizic acid (Na 2 GA). The compositions were studied in the solid phase by means of scanning electron microscopy, powder X-ray diffraction and thermal analysis, and in solutions by means of HPLC, gel permeation chromatography, phase solubility assay and 1 H NMR spectroscopy. PZQ permeability was studied by means of parallel artificial membrane permeability assay and with a monolayer of Caco-2 cells. The pharmacokinetic characteristics and acute toxicity of PZQ and its compositions were studied on mice. Solubility of PZQ in the compositions increases up to 3.5 times. The micelles in Na 2 GA solutions possess a molecular mass of ~60 kDa. An increase in PZQ solubility may be due to its inclusion into micelles of glycyrrhizic acid. The permeability of PZQ was found to be much higher from its composition with Na 2 GA in comparison with initial PZQ. An increase in PZQ bioavailability by a factor of 3 in laboratory mice and changes of pharmacokinetic curve shape were demonstrated for the oral administration of its composition with Na 2 GA. The solid compositions show high chemical stability under rapid storage test. The obtained PZQ compositions may be a promising basis for the development of anthelmintic preparations with increased efficiency.
Journal of Agricultural and Food Chemistry, 2017
To increase the bioavailability of plant protection products we have applied new approach based o... more To increase the bioavailability of plant protection products we have applied new approach based on non-covalent association with natural water soluble polysaccharides and oligosaccharides as delivery systems (DSs). The mechanochemical technique has been applied to prepare the solid state nano-dispersed compositions of antidote 1,8-naphthalic anhydride (NA) with arabinogalactan, sodium salt of carboxymethylcellulose, and glycyrrhizin as DSs. The effect of DSs on the solubility and the penetration of NA into the seeds of barley and wheat has been investigated by various physicochemical techniques. All DSs considerably enhance the solubility of NA and improve its penetration into the grain. The influence of polysaccharides and oligosaccharides on artificial lipid membrane was studied by NMR relaxation method. It was concluded, that the effect of polysaccharides and oligosaccharides on the penetration efficacy of plant protection products might be associated with the detected solubility enhancement and the affinity of DSs to the surface of cell membranes.
Russian Chemical Bulletin, 2017
Glycyrrhizic acid, arabinogalactan, and β cyclodextrin are capable of forming complexes with vari... more Glycyrrhizic acid, arabinogalactan, and β cyclodextrin are capable of forming complexes with various drug compounds significantly enhancing their solubility and bioavailability. To elucidate the mechanism of action of oligo and polysaccharides, the exchange time of transporting formate ions through the membrane of myeloblastic leukemia cells (K562) was measured by NMR spectroscopy with the addition of paramagnetic ions. It was found that glycyrrhizic acid and arabinogalactan substantially increased the membrane permeability.