The sour cherry contains anthocyanins, which have bactericide action against some oral bacteria (... more The sour cherry contains anthocyanins, which have bactericide action against some oral bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa). Sour cherry also has antibiofilm action against Streptococcus mutans, Candida albicans, and Fusobacterium nucleatum. Our earlier research proved that chewing sour cherry anthocyanin gum significantly reduces the amount of human salivary alpha-amylase and Streptococcus mutans levels. The microbiota of a toothbrush affects oral health and regular toothbrush change is recommended. A total of 20 healthy participants were selected for the study. We analysed saliva samples with 16S rRNA sequencing to investigate the effect of 2 weeks (daily three times, after main meals) of chewing sour cherry anthocyanin gum—supplemented by toothbrush change in half of our case–control study cohort—after scaling on human oral microbiota. A more stable and diverse microbiome could be observed after scaling by the anthocyanin gum. Significant differences between g...
The antimicrobial effect of chitosan and synthetic chitosan derivatives has been confirmed on man... more The antimicrobial effect of chitosan and synthetic chitosan derivatives has been confirmed on many Gram-positive and Gram-negative bacteria and fungi. The tests were carried out on pathogenic microorganisms, so the mechanism and concentration dependence of the inhibitory effect of chitosan were revealed. We conducted our tests on a probiotic strain, Lactobacillus plantarum. Commercially available chitosan derivatives of different molecular weights were added to L. plantarum suspension in increasing concentrations. The minimum inhibitory concentration (MIC) value of chitosan was determined and confirmed the viability decreasing effect at concentrations above the MIC with a time-kill assay. The release of bacterium cell content was measured at 260 nm after treatment with 0.001–0.1% concentration chitosan solution. An increase in the permeability of the cell membrane was observed only with the 0.1% treatment. The interaction was also investigated by zeta potential measurement, and the ...
Gastroretentive systems may overcome problems associated with incomplete drug absorption by local... more Gastroretentive systems may overcome problems associated with incomplete drug absorption by localized release of the API in the stomach. Low-density drug delivery systems can float in the gastric content and improve the bioavailability of small molecules. The current publication presents verapamil–HCl-containing solid foam prepared by continuous manufacturing. Production runs were validated, and the foam structure was characterized by micro-CT scans and SEM. Dissolution properties, texture changes during dissolution, and floating forces were analyzed. An optimized formulation was chosen and given orally to Beagle dogs to determine the pharmacokinetic parameters of the solid foam capsules. As a result, a 12.5 m/m% stearic acid content was found to be the most effective to reduce the apparent density of capsules. Drug release can be described by the first-order model, where 70% of verapamil dissolved after 10 h from the optimized formulation. The texture analysis proved that the struc...
Turmeric has been used for decades for its antioxidant and anti-inflammatory effect, which is due... more Turmeric has been used for decades for its antioxidant and anti-inflammatory effect, which is due to an active ingredient isolated from the plant, called curcumin. However, the extremely poor water-solubility of curcumin often limits the bioavailability of the drug. The aim of our experimental work was to improve the solubility and thus bioavailability of curcumin by developing self-nano/microemulsifying drug delivery systems (SN/MEDDS). Labrasol and Cremophor RH 40 as nonionic surfactants, Transcutol P as co-surfactant and isopropyl myristate as the oily phase were used during the formulation. The average droplet size of SN/MEDDS containing curcumin was between 32 and 405 nm. It was found that the higher oil content resulted in larger particle size. The drug loading efficiency was between 93.11% and 99.12% and all formulations were thermodynamically stable. The curcumin release was studied at pH 6.8, and the release efficiency ranged between 57.3% and 80.9% after 180 min. The resul...
Philadelphus coronarius is a versatile plant and its use in folk medicine has a long tradition; h... more Philadelphus coronarius is a versatile plant and its use in folk medicine has a long tradition; however, scientifically, the medical utilization of the herb is a less explored research field. The aim of our study was to identify and determine the quantity of the bioactive compounds of both the leaf and the flower and prepare a lyophilized product of them, from which medical ointments were formulated, since the topical application of P. coronarius has also not been studied. In vitro drug release, texture analysis and biocompatibility experiments were carried out, as well as the investigation of microbiological, antioxidant and anti-inflammatory properties. According to our results the composition and the selected excipients of the ointments have a great impact on the drug release, texture and bioavailability of the preparation. During the microbiological testing, the P. coronarius leaf was effective against Escherichia coli and Staphylococcus aureus, but it did not significantly decr...
Increased permeability of the epithelial and endothelial cell layers results in the onset of path... more Increased permeability of the epithelial and endothelial cell layers results in the onset of pathogenic mechanisms. In both cell types, cell–cell connections play a regulatory role in altering membrane permeability. The aim of this study was to investigate the modulating effect of anthocyanin-rich extract (AC) on TJ proteins in inflammatory Caco-2 and HUVEC monolayers. Distribution of Occludin and zonula occludens-1 (ZO-1) were investigated by immunohistochemical staining and the protein levels were measured by flow cytometry. The mRNA expression was determined by quantitative real-time PCR. The transepithelial electrical resistance (TEER) values were measured during a permeability assay on HUVEC cell culture. As a result of inflammatory induction by TNF-α, redistribution of proteins was observed in Caco-2 cell culture, which was reduced by AC treatment. In HUVEC cell culture, the decrease in protein and mRNA expression was more dominant during inflammatory induction, which was comp...
Diabetic retinopathy (DR) is a neurovascular disease characterized by the reduction of retina int... more Diabetic retinopathy (DR) is a neurovascular disease characterized by the reduction of retina integrity and functionality, as a consequence of retinal pigment epithelial cell fibrosis. Although galectin-1 (a glycan-binding protein) has been associated with dysregulated retinal angiogenesis, no evidence has been reported about galectin-1 roles in DR-induced fibrosis. ARPE-19 cells were cultured in normal (5 mM) or high glucose (35 mM) for 3 days, then exposed to the selective galectin-1 inhibitor OTX008 (2.5–5–10 μM) for 6 days. The determination of cell viability and ROS content along with the analysis of specific proteins (by immunocytochemistry, Western blotting, and ELISA) or mRNAs (by real time-PCR) were performed. OTX008 5 μM and 10 μM improved cell viability and markedly reduced galectin-1 protein expression in cells exposed to high glucose. This was paralleled by a down-regulation of the TGF-β/, NF-kB p65 levels, and ROS content. Moreover, epithelial–mesenchymal transition ma...
The investigation of the usability of solid insoluble β-cyclodextrin polymers (βCDP) in micro-siz... more The investigation of the usability of solid insoluble β-cyclodextrin polymers (βCDP) in micro-sized, controlled drug delivery systems has only recently attracted interest. Our aim was to form complexes with poorly soluble active pharmaceutical ingredients (APIs) with two types of βCDP for drug delivery applications. Solid insoluble cyclodextrin polymer of irregular shape (βCDPIS) and cyclodextrin microbeads (βCDPB) were used in the experiments. Morphology, surface area, size distribution and swelling capacity of carriers were investigated. We created complexes with two APIs, curcumin and estradiol, and applied powder X-ray diffraction, FTIR and thermal analysis (TGA/DSC) to prove the complexation. Finally, the dissolution, biocompatibility and permeation of APIs on Caco-2 cells were investigated. The size of the beads was larger than 100 µm, their shape was spherical and surfaces were smooth; while the βCDPIS particles were around 4 µm with irregular shape and surface. None of the p...
The rapid progress in biotechnology over the past few decades has accelerated the large-scale pro... more The rapid progress in biotechnology over the past few decades has accelerated the large-scale production of therapeutic peptides and proteins, making them available in medical practice. However, injections are the most common method of administration; these procedures might lead to inconvenience. Non-invasive medications, such as oral administration of bio-compounds, can reduce or eliminate pain and increase safety. The aim of this project was to develop and characterize novel melanin concentrating hormone (MCH) formulations for oral administration. As a drug delivery system, penetration enhancer combined alginate beads were formulated and characterized. The combination of alginate carriers with amphiphilic surfactants has not been described yet. Due to biosafety having high priority in the case of novel pharmaceutical formulations, the biocompatibility of selected auxiliary materials and their combinations was evaluated using different in vitro methods. Excipients were selected acc...
Cyclodextrins are high molecular weight, hydrophilic, cyclic, non-reducing oligosaccharides, appl... more Cyclodextrins are high molecular weight, hydrophilic, cyclic, non-reducing oligosaccharides, applied as excipients for the improvement of the solubility and permeability of insoluble active pharmaceutical ingredients. On the other hand, beta-cyclodextrins are used as cholesterol sequestering agents in life sciences. Recently, we demonstrated the cellular internalization and intracellular effects of cyclodextrins on Caco-2 cells. In this study, we aimed to further investigate the endocytosis of (2-hydroxylpropyl)-beta-(HPBCD) and random methylated-beta-cyclodextrin (RAMEB) to test their cytotoxicity, NF-kappa B pathway induction, autophagy, and lysosome formation on HeLa cells. These derivatives were able to enter the cells; however, major differences were revealed in the inhibition of their endocytosis compared to Caco-2 cells. NF-kappa B p65 translocation was not detected in the cell nuclei after HPBCD or RAMEB pre-treatment and cyclodextrin treatment did not enhance the formation ...
Nowadays, polyethylene glycols referred to as PEGs are widely used in cosmetics, consumer care pr... more Nowadays, polyethylene glycols referred to as PEGs are widely used in cosmetics, consumer care products, and the pharmaceutical industry. Their advantageous properties such as chemical stability, low immunogenicity, and high tolerability explain why PEGs are applied in many fields of pharmaceutical formulations including parenteral, topical, ophthalmic, oral, and rectal preparations and also in modern drug delivery systems. Given their extensive use, they are considered a well-known group of chemicals. However, the number of large-scale comparative studies involving multiple PEGs of wide molecular weight range is low, as in most cases biological effects are estimated upon molecular weight. The aim of this publication was to study the action of PEGs on Caco-2 cells and G. mellonella larvae and to calculate the correlation of these effects with molecular weight and osmolality. Eleven PEGs of different molecular weight were used in our experiments: PEG 200, PEG 300, PEG 400, PEG 600, P...
The blood-brain barrier (BBB), an interface between the systemic circulation and the nervous syst... more The blood-brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide α-MSH on a culture model of the BBB, primary rat brain endothelial cells co-cultured with rat brain pericytes and glial cells. We demonstrated the expression of melanocortin-1 receptor in isolated rat brain...
International journal of pharmaceutics, Jan 21, 2015
Cyclodextrins are widely used excipients in pharmaceutical formulations. They are mainly utilized... more Cyclodextrins are widely used excipients in pharmaceutical formulations. They are mainly utilized as solubilizers and absorption enhancers, but recent results revealed their effects on cell membranes and pharmacological barriers. In addition to the growing knowledge on their interaction with plasma membranes, it was confirmed that cyclodextrins are able to enter cells by endocytosis. The number of the tested cyclodextrins was limited, and the role of this mechanism in drug absorption and delivery is not known. Our aim was to examine the endocytosis of fluorescently labeled hydroxypropyl-β-cyclodextrin, random methyl-β-cyclodextrin and soluble β-cyclodextrin polymer, and the cellular uptake of the fluorescent paclitaxel derivative-random methyl-β-cyclodextrin complex. The studied cyclodextrin derivatives were able to enter Caco-2 intestinal cells and localized in vesicles in the cytoplasm, while their permeability was very limited through Caco-2 monolayers. We demonstrated for the fi...
American Journal of Physiology-Heart and Circulatory Physiology, 2006
The effects of kernel extract obtained from sour cherry ( Prunus cerasus) seed on the postischemi... more The effects of kernel extract obtained from sour cherry ( Prunus cerasus) seed on the postischemic cardiac recovery were studied in isolated working rat hearts. Rats were treated with various daily doses of the extract for 14 days, and hearts were then isolated and subjected to 30 min of global ischemia followed by 120 min of reperfusion. The incidence of ventricular fibrillation (VF) and tachycardia (VT) fell from their control values of 92% and 100% to 50% (not significant) and 58% (not significant), 17% ( P < 0.05), and 25% ( P < 0.05) with the doses of 10 mg/kg and 30 mg/kg of the extract, respectively. Lower concentrations of the extract (1 and 5 mg/kg) failed to significantly reduce the incidence of VF and VT during reperfusion. Sour cherry seed kernel extract (10 and 30 mg/kg) significantly improved the postischemic recovery of cardiac function (coronary flow, aortic flow, and left ventricular developed pressure) during reperfusion. We have also demonstrated that the ex...
Microencapsulation and coating are preferred methods to increase the viability of the probiotic s... more Microencapsulation and coating are preferred methods to increase the viability of the probiotic strains. The effect of microencapsulation technologies and materials used as microcapsule cores on viability is being investigated during development. In the present study, chitosan-coated and Eudragit L100-55-coated alginate microspheres were produced to encapsulate Lactobacillus plantarum probiotic bacteria. After the heat loading and simulated gastrointestinal juice dissolution study, the differences in viability were compared based on the CFU/mL values of the samples. The kinetics of the bacterial release and the ratio of the released live/dead cells of Lactobacillus plantarum were examined by flow cytometry. In all cases, we found that the CFU value for the chitosan-coated samples was virtually zero. The ratio of live/dead cells in the 120 min samples was significantly reduced to less than 20% for chitosan, while it was nearly 90% in the uncoated and Eudragit L100-55-coated samples. ...
Through the twentieth century, the road from synthetizing a new drug molecule to become an actual... more Through the twentieth century, the road from synthetizing a new drug molecule to become an actual product got longer than ever before. Cytotoxicity assays are a quick way to assess a certain chemical compound’s effects on a given human cell line. The most well-known techniques are the MTTand the LDH-assays. These tests are cheap, easy to execute, but not very precise and dependent on various environmental factors and also, they show no detail about the time-dependency of the toxic effect. Cytotoxicity experiments are a crucial part of a modern pharmaceutical development process. They are a cheap and safe way to get vital information about a new molecule’s biological attributes focusing on its basic tolerability. These studies not only save human lives and test animals, but they save the time and resources to be spared on a test molecule which is a complete failure having no in vitro safety.
The sour cherry contains anthocyanins, which have bactericide action against some oral bacteria (... more The sour cherry contains anthocyanins, which have bactericide action against some oral bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa). Sour cherry also has antibiofilm action against Streptococcus mutans, Candida albicans, and Fusobacterium nucleatum. Our earlier research proved that chewing sour cherry anthocyanin gum significantly reduces the amount of human salivary alpha-amylase and Streptococcus mutans levels. The microbiota of a toothbrush affects oral health and regular toothbrush change is recommended. A total of 20 healthy participants were selected for the study. We analysed saliva samples with 16S rRNA sequencing to investigate the effect of 2 weeks (daily three times, after main meals) of chewing sour cherry anthocyanin gum—supplemented by toothbrush change in half of our case–control study cohort—after scaling on human oral microbiota. A more stable and diverse microbiome could be observed after scaling by the anthocyanin gum. Significant differences between g...
The antimicrobial effect of chitosan and synthetic chitosan derivatives has been confirmed on man... more The antimicrobial effect of chitosan and synthetic chitosan derivatives has been confirmed on many Gram-positive and Gram-negative bacteria and fungi. The tests were carried out on pathogenic microorganisms, so the mechanism and concentration dependence of the inhibitory effect of chitosan were revealed. We conducted our tests on a probiotic strain, Lactobacillus plantarum. Commercially available chitosan derivatives of different molecular weights were added to L. plantarum suspension in increasing concentrations. The minimum inhibitory concentration (MIC) value of chitosan was determined and confirmed the viability decreasing effect at concentrations above the MIC with a time-kill assay. The release of bacterium cell content was measured at 260 nm after treatment with 0.001–0.1% concentration chitosan solution. An increase in the permeability of the cell membrane was observed only with the 0.1% treatment. The interaction was also investigated by zeta potential measurement, and the ...
Gastroretentive systems may overcome problems associated with incomplete drug absorption by local... more Gastroretentive systems may overcome problems associated with incomplete drug absorption by localized release of the API in the stomach. Low-density drug delivery systems can float in the gastric content and improve the bioavailability of small molecules. The current publication presents verapamil–HCl-containing solid foam prepared by continuous manufacturing. Production runs were validated, and the foam structure was characterized by micro-CT scans and SEM. Dissolution properties, texture changes during dissolution, and floating forces were analyzed. An optimized formulation was chosen and given orally to Beagle dogs to determine the pharmacokinetic parameters of the solid foam capsules. As a result, a 12.5 m/m% stearic acid content was found to be the most effective to reduce the apparent density of capsules. Drug release can be described by the first-order model, where 70% of verapamil dissolved after 10 h from the optimized formulation. The texture analysis proved that the struc...
Turmeric has been used for decades for its antioxidant and anti-inflammatory effect, which is due... more Turmeric has been used for decades for its antioxidant and anti-inflammatory effect, which is due to an active ingredient isolated from the plant, called curcumin. However, the extremely poor water-solubility of curcumin often limits the bioavailability of the drug. The aim of our experimental work was to improve the solubility and thus bioavailability of curcumin by developing self-nano/microemulsifying drug delivery systems (SN/MEDDS). Labrasol and Cremophor RH 40 as nonionic surfactants, Transcutol P as co-surfactant and isopropyl myristate as the oily phase were used during the formulation. The average droplet size of SN/MEDDS containing curcumin was between 32 and 405 nm. It was found that the higher oil content resulted in larger particle size. The drug loading efficiency was between 93.11% and 99.12% and all formulations were thermodynamically stable. The curcumin release was studied at pH 6.8, and the release efficiency ranged between 57.3% and 80.9% after 180 min. The resul...
Philadelphus coronarius is a versatile plant and its use in folk medicine has a long tradition; h... more Philadelphus coronarius is a versatile plant and its use in folk medicine has a long tradition; however, scientifically, the medical utilization of the herb is a less explored research field. The aim of our study was to identify and determine the quantity of the bioactive compounds of both the leaf and the flower and prepare a lyophilized product of them, from which medical ointments were formulated, since the topical application of P. coronarius has also not been studied. In vitro drug release, texture analysis and biocompatibility experiments were carried out, as well as the investigation of microbiological, antioxidant and anti-inflammatory properties. According to our results the composition and the selected excipients of the ointments have a great impact on the drug release, texture and bioavailability of the preparation. During the microbiological testing, the P. coronarius leaf was effective against Escherichia coli and Staphylococcus aureus, but it did not significantly decr...
Increased permeability of the epithelial and endothelial cell layers results in the onset of path... more Increased permeability of the epithelial and endothelial cell layers results in the onset of pathogenic mechanisms. In both cell types, cell–cell connections play a regulatory role in altering membrane permeability. The aim of this study was to investigate the modulating effect of anthocyanin-rich extract (AC) on TJ proteins in inflammatory Caco-2 and HUVEC monolayers. Distribution of Occludin and zonula occludens-1 (ZO-1) were investigated by immunohistochemical staining and the protein levels were measured by flow cytometry. The mRNA expression was determined by quantitative real-time PCR. The transepithelial electrical resistance (TEER) values were measured during a permeability assay on HUVEC cell culture. As a result of inflammatory induction by TNF-α, redistribution of proteins was observed in Caco-2 cell culture, which was reduced by AC treatment. In HUVEC cell culture, the decrease in protein and mRNA expression was more dominant during inflammatory induction, which was comp...
Diabetic retinopathy (DR) is a neurovascular disease characterized by the reduction of retina int... more Diabetic retinopathy (DR) is a neurovascular disease characterized by the reduction of retina integrity and functionality, as a consequence of retinal pigment epithelial cell fibrosis. Although galectin-1 (a glycan-binding protein) has been associated with dysregulated retinal angiogenesis, no evidence has been reported about galectin-1 roles in DR-induced fibrosis. ARPE-19 cells were cultured in normal (5 mM) or high glucose (35 mM) for 3 days, then exposed to the selective galectin-1 inhibitor OTX008 (2.5–5–10 μM) for 6 days. The determination of cell viability and ROS content along with the analysis of specific proteins (by immunocytochemistry, Western blotting, and ELISA) or mRNAs (by real time-PCR) were performed. OTX008 5 μM and 10 μM improved cell viability and markedly reduced galectin-1 protein expression in cells exposed to high glucose. This was paralleled by a down-regulation of the TGF-β/, NF-kB p65 levels, and ROS content. Moreover, epithelial–mesenchymal transition ma...
The investigation of the usability of solid insoluble β-cyclodextrin polymers (βCDP) in micro-siz... more The investigation of the usability of solid insoluble β-cyclodextrin polymers (βCDP) in micro-sized, controlled drug delivery systems has only recently attracted interest. Our aim was to form complexes with poorly soluble active pharmaceutical ingredients (APIs) with two types of βCDP for drug delivery applications. Solid insoluble cyclodextrin polymer of irregular shape (βCDPIS) and cyclodextrin microbeads (βCDPB) were used in the experiments. Morphology, surface area, size distribution and swelling capacity of carriers were investigated. We created complexes with two APIs, curcumin and estradiol, and applied powder X-ray diffraction, FTIR and thermal analysis (TGA/DSC) to prove the complexation. Finally, the dissolution, biocompatibility and permeation of APIs on Caco-2 cells were investigated. The size of the beads was larger than 100 µm, their shape was spherical and surfaces were smooth; while the βCDPIS particles were around 4 µm with irregular shape and surface. None of the p...
The rapid progress in biotechnology over the past few decades has accelerated the large-scale pro... more The rapid progress in biotechnology over the past few decades has accelerated the large-scale production of therapeutic peptides and proteins, making them available in medical practice. However, injections are the most common method of administration; these procedures might lead to inconvenience. Non-invasive medications, such as oral administration of bio-compounds, can reduce or eliminate pain and increase safety. The aim of this project was to develop and characterize novel melanin concentrating hormone (MCH) formulations for oral administration. As a drug delivery system, penetration enhancer combined alginate beads were formulated and characterized. The combination of alginate carriers with amphiphilic surfactants has not been described yet. Due to biosafety having high priority in the case of novel pharmaceutical formulations, the biocompatibility of selected auxiliary materials and their combinations was evaluated using different in vitro methods. Excipients were selected acc...
Cyclodextrins are high molecular weight, hydrophilic, cyclic, non-reducing oligosaccharides, appl... more Cyclodextrins are high molecular weight, hydrophilic, cyclic, non-reducing oligosaccharides, applied as excipients for the improvement of the solubility and permeability of insoluble active pharmaceutical ingredients. On the other hand, beta-cyclodextrins are used as cholesterol sequestering agents in life sciences. Recently, we demonstrated the cellular internalization and intracellular effects of cyclodextrins on Caco-2 cells. In this study, we aimed to further investigate the endocytosis of (2-hydroxylpropyl)-beta-(HPBCD) and random methylated-beta-cyclodextrin (RAMEB) to test their cytotoxicity, NF-kappa B pathway induction, autophagy, and lysosome formation on HeLa cells. These derivatives were able to enter the cells; however, major differences were revealed in the inhibition of their endocytosis compared to Caco-2 cells. NF-kappa B p65 translocation was not detected in the cell nuclei after HPBCD or RAMEB pre-treatment and cyclodextrin treatment did not enhance the formation ...
Nowadays, polyethylene glycols referred to as PEGs are widely used in cosmetics, consumer care pr... more Nowadays, polyethylene glycols referred to as PEGs are widely used in cosmetics, consumer care products, and the pharmaceutical industry. Their advantageous properties such as chemical stability, low immunogenicity, and high tolerability explain why PEGs are applied in many fields of pharmaceutical formulations including parenteral, topical, ophthalmic, oral, and rectal preparations and also in modern drug delivery systems. Given their extensive use, they are considered a well-known group of chemicals. However, the number of large-scale comparative studies involving multiple PEGs of wide molecular weight range is low, as in most cases biological effects are estimated upon molecular weight. The aim of this publication was to study the action of PEGs on Caco-2 cells and G. mellonella larvae and to calculate the correlation of these effects with molecular weight and osmolality. Eleven PEGs of different molecular weight were used in our experiments: PEG 200, PEG 300, PEG 400, PEG 600, P...
The blood-brain barrier (BBB), an interface between the systemic circulation and the nervous syst... more The blood-brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide α-MSH on a culture model of the BBB, primary rat brain endothelial cells co-cultured with rat brain pericytes and glial cells. We demonstrated the expression of melanocortin-1 receptor in isolated rat brain...
International journal of pharmaceutics, Jan 21, 2015
Cyclodextrins are widely used excipients in pharmaceutical formulations. They are mainly utilized... more Cyclodextrins are widely used excipients in pharmaceutical formulations. They are mainly utilized as solubilizers and absorption enhancers, but recent results revealed their effects on cell membranes and pharmacological barriers. In addition to the growing knowledge on their interaction with plasma membranes, it was confirmed that cyclodextrins are able to enter cells by endocytosis. The number of the tested cyclodextrins was limited, and the role of this mechanism in drug absorption and delivery is not known. Our aim was to examine the endocytosis of fluorescently labeled hydroxypropyl-β-cyclodextrin, random methyl-β-cyclodextrin and soluble β-cyclodextrin polymer, and the cellular uptake of the fluorescent paclitaxel derivative-random methyl-β-cyclodextrin complex. The studied cyclodextrin derivatives were able to enter Caco-2 intestinal cells and localized in vesicles in the cytoplasm, while their permeability was very limited through Caco-2 monolayers. We demonstrated for the fi...
American Journal of Physiology-Heart and Circulatory Physiology, 2006
The effects of kernel extract obtained from sour cherry ( Prunus cerasus) seed on the postischemi... more The effects of kernel extract obtained from sour cherry ( Prunus cerasus) seed on the postischemic cardiac recovery were studied in isolated working rat hearts. Rats were treated with various daily doses of the extract for 14 days, and hearts were then isolated and subjected to 30 min of global ischemia followed by 120 min of reperfusion. The incidence of ventricular fibrillation (VF) and tachycardia (VT) fell from their control values of 92% and 100% to 50% (not significant) and 58% (not significant), 17% ( P < 0.05), and 25% ( P < 0.05) with the doses of 10 mg/kg and 30 mg/kg of the extract, respectively. Lower concentrations of the extract (1 and 5 mg/kg) failed to significantly reduce the incidence of VF and VT during reperfusion. Sour cherry seed kernel extract (10 and 30 mg/kg) significantly improved the postischemic recovery of cardiac function (coronary flow, aortic flow, and left ventricular developed pressure) during reperfusion. We have also demonstrated that the ex...
Microencapsulation and coating are preferred methods to increase the viability of the probiotic s... more Microencapsulation and coating are preferred methods to increase the viability of the probiotic strains. The effect of microencapsulation technologies and materials used as microcapsule cores on viability is being investigated during development. In the present study, chitosan-coated and Eudragit L100-55-coated alginate microspheres were produced to encapsulate Lactobacillus plantarum probiotic bacteria. After the heat loading and simulated gastrointestinal juice dissolution study, the differences in viability were compared based on the CFU/mL values of the samples. The kinetics of the bacterial release and the ratio of the released live/dead cells of Lactobacillus plantarum were examined by flow cytometry. In all cases, we found that the CFU value for the chitosan-coated samples was virtually zero. The ratio of live/dead cells in the 120 min samples was significantly reduced to less than 20% for chitosan, while it was nearly 90% in the uncoated and Eudragit L100-55-coated samples. ...
Through the twentieth century, the road from synthetizing a new drug molecule to become an actual... more Through the twentieth century, the road from synthetizing a new drug molecule to become an actual product got longer than ever before. Cytotoxicity assays are a quick way to assess a certain chemical compound’s effects on a given human cell line. The most well-known techniques are the MTTand the LDH-assays. These tests are cheap, easy to execute, but not very precise and dependent on various environmental factors and also, they show no detail about the time-dependency of the toxic effect. Cytotoxicity experiments are a crucial part of a modern pharmaceutical development process. They are a cheap and safe way to get vital information about a new molecule’s biological attributes focusing on its basic tolerability. These studies not only save human lives and test animals, but they save the time and resources to be spared on a test molecule which is a complete failure having no in vitro safety.
Uploads
Papers by Judit Váradi