TY - JOUR AU - Herczeg, Mihály AU - Demeter, Fruzsina AU - Nagy, Tibor AU - Rusznyák, Ágnes AU - Hodek, Jan AU - Sipos, Éva AU - Lekli, István AU - Fenyvesi, Ferenc AU - Weber, Jan AU - Kéki, Sándor AU - Borbás, Anikó TI - Block Synthesis and Step-Growth Polymerization of C-6-Sulfonatomethyl-Containing Sulfated Malto-Oligosaccharides and Their Biological Profiling JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 1 SN - 1661-6596 DO - 10.3390/ijms25010677 UR - https://m2.mtmt.hu/api/publication/34502650 ID - 34502650 AB - Highly sulfated malto-oligomers, similar to heparin and heparan-sulfate, have good antiviral, antimetastatic, anti-inflammatory and cell growth inhibitory effects. Due to their broad biological activities and simple structure, sulfated malto-oligomer derivatives have a great therapeutic potential, therefore, the development of efficient synthesis methods for their production is of utmost importance. In this work, preparation of α-(1→4)-linked oligoglucosides containing a sulfonatomethyl moiety at position C-6 of each glucose unit was studied by different approaches. Malto-oligomeric sulfonic acid derivatives up to dodecasaccharides were prepared by polymerization using different protecting groups, and the composition of the product mixtures was analyzed by MALDI-MS methods and size-exclusion chromatography. Synthesis of lower oligomers was also accomplished by stepwise and block synthetic methods, and then the oligosaccharide products were persulfated. The antiviral, anti-inflammatory and cell growth inhibitory activity of the fully sulfated malto-oligosaccharide sulfonic acids were determined by in vitro tests. Four tested di- and trisaccharide sulfonic acids effectively inhibited the activation of the TNF-α-mediated inflammatory pathway without showing cytotoxicity. LA - English DB - MTMT ER - TY - JOUR AU - Szőke, Kitti AU - Kajtár, Richárd AU - Gyöngyösi, Alexandra AU - Czompa, Attila AU - Fésüs, Adina AU - Lőrincz, Eszter Boglárka AU - Petróczi, Ferenc Dániel AU - Herczegh, Pál AU - Bak, István AU - Borbás, Anikó AU - Bakai-Bereczki, Ilona AU - Lekli, István TI - Pharmacological Evaluation of Newly Synthesized Cannabidiol Derivates on H9c2 Cells JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 12 PY - 2023 IS - 9 PG - 15 SN - 2076-3921 DO - 10.3390/antiox12091714 UR - https://m2.mtmt.hu/api/publication/34125145 ID - 34125145 LA - English DB - MTMT ER - TY - JOUR AU - Frei, Gréta AU - Haimhoffer, Ádám AU - Csapó, Enikő AU - Bodnár, Krisztina AU - Vasvári, Gábor AU - Nemes, Dániel AU - Lekli, István AU - Gyöngyösi, Alexandra AU - Bácskay, Ildikó AU - Siposné Fehér, Pálma AU - Józsa, Liza TI - In Vitro and In Vivo Efficacy of Topical Dosage Forms Containing Self-Nanoemulsifying Drug Delivery System Loaded with Curcumin JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 8 SP - 2054 SN - 1999-4923 DO - 10.3390/pharmaceutics15082054 UR - https://m2.mtmt.hu/api/publication/34124819 ID - 34124819 AB - The external use of curcumin is rare, although it can be a valuable active ingredient in the treatment of certain inflammatory diseases. The aim of our experimental work was to formulate topical dosage forms containing curcumin for the treatment of atopic dermatitis. Curcumin has extremely poor solubility and bioavailability, so we have tried to increase it with the usage of self-emulsifying drug delivery systems. Creams and gels were formulated using penetration-enhancing surfactants and gelling agents. The release of the drug from the vehicle and its penetration through the membrane were determined using a Franz diffusion cell. An MTT cytotoxicity and in vitro antioxidant assays were performed on HaCaT cell line. The in vivo anti-inflammatory effect of the preparations was tested by measuring rat paw edema. In addition, we examined the degree of inflammation induced by UV radiation after pretreatment with the cream and the gel on rats. For the gels containing SNEDDS, the highest penetration was measured after half an hour, while for the cream, it took one hour to reach the maximum concentration. The gel containing Pemulen TR-1 showed the highest drug release. It was determined that the curcumin-containing preparations can be safely applied on the skin and have antioxidant effects. The animal experiments have proven the effectiveness of curcumin-containing topical preparations. LA - English DB - MTMT ER - TY - JOUR AU - To Quoc, Thinh AU - Bíró, Krisztina AU - Pető, Ágota AU - Kósa, Dóra AU - Sinka, Dávid AU - Lekli, István AU - Kiss, Attila AU - Budai, István AU - Béresová, Monika AU - Vecsernyés, Miklós AU - Siposné Fehér, Pálma AU - Bácskay, Ildikó AU - Ujhelyi, Zoltán TI - Development and Evaluation of an FDM Printed Nasal Device for CPZ Solid Nanoparticles JF - MOLECULES J2 - MOLECULES VL - 28 PY - 2023 IS - 11 PG - 15 SN - 1420-3049 DO - 10.3390/molecules28114406 UR - https://m2.mtmt.hu/api/publication/33938541 ID - 33938541 AB - Nasal drug delivery has been a focus of scientific interest for decades. A number of drug delivery systems and devices are available and have been highly successful in providing better and more comfortable therapy. The benefits of nasal drug delivery are not in question. The nasal surface provides an excellent context for the targeted delivery of active substances. In addition to the large nasal surface area and intensive absorption, the active substances delivered through the nose overcome the blood–brain barrier and can be delivered directly to the central nervous system. Formulations for nasal administration are typically solutions or liquid dispersed systems such as emulsions or suspensions. Formulation techniques for nanostructures have recently undergone intensive development. Solid-phase heterogeneous dispersed systems represent a new direction in pharmaceutical formulations. The wide range of possible examples and the variety of excipients allow for the delivery of a wide range of active ingredients. The aim of our experimental work was to develop a solid drug delivery system that possesses all of the above-mentioned advantageous properties. In developing solid nanosystems, we not only exploited the advantages of size but also the adhesive and penetration-enhancing properties of excipients. During formulation, several amphiphilic compounds with adhesion properties and penetration enhancing effects were incorporated. We used chlorpromazine (CPZ), which is mainly used in the treatment of psychotic disorders such as schizophrenia and bipolar disorder. Chlorpromazine has been previously investigated by our team in other projects. With the availability of previous methods, the analytical characterization of the drug was carried out effectively. Due to the frequent and severe side effects of the drug, the need for therapeutic dose reduction is indisputable. In this series of experiments, we succeeded in constructing drug delivery systems. Finely divided Na nanoparticles were formed using a Büchi B90 nanospray dryer. An important step in the development of the drug carrier was the selection of suitable inert carrier compounds. Particle size determination and particle size distribution analysis were performed to characterize the prepared nanostructures. As safety is the most important aspect of any drug formulation, all components and systems were tested with different biocompatibility assays. The tests performed demonstrated the safe applicability of our systems. The bioavailability of chlorpromazine was studied as a function of the ratio of the active ingredient administered nasally and intravenously. As described above, most nasal formulations are liquids, but our system is solid, so there is currently no tool available to accurately target this system. As a supplement of the project, a nasal dosing device was developed, corresponding to the anatomical structure; a prototype of the device was made using 3D FDM technology. Our results lay the foundation for the design and industrial scaling of a new approach to the design and production of a high-bioavailability nasal medicinal product. LA - English DB - MTMT ER - TY - JOUR AU - Szőke, Kitti AU - Bódi, Beáta AU - Hendrik, Zoltán AU - Czompa, Attila AU - Gyöngyösi, Alexandra AU - Haines, Donald David AU - Papp, Zoltán AU - Tósaki, Árpád AU - Lekli, István TI - Rapamycin treatment increases survival, autophagy biomarkers and expression of the anti‐aging klotho protein in elderly mice JF - PHARMACOLOGY RESEARCH AND PERSPECTIVES J2 - PHARMACOL RES PERSPECT VL - 11 PY - 2023 IS - 3 PG - 11 SN - 2052-1707 DO - 10.1002/prp2.1091 UR - https://m2.mtmt.hu/api/publication/33828248 ID - 33828248 AB - Previous investigations have demonstrated that treatment of animals with rapamycin increases levels of autophagy, which is a process by which cells degrade intracellular detritus, thus suppressing the emergence of senescent cells, whose pro-inflammatory properties, are primary drivers of age-associated physical decline. A hypothesis is tested here that rapamycin treatment of mice approaching the end of their normal lifespan exhibits increased survival, enhanced expression of autophagic proteins; and klotho protein—a biomarker of aging that affects whole organism senescence, and systemic suppression of inflammatory mediator production. Test groups of 24-month-old C57BL mice were injected intraperitoneally with either 1.5 mg/kg/week rapamycin or vehicle. All mice administered rapamycin survived the 12-week course, whereas 43% of the controls died. Relative to controls, rapamycin-treated mice experienced minor but significant weight loss; moreover, nonsignificant trends toward decreased levels of leptin, IL-6, IL-1β, TNF-α, IL-1α, and IGF-1, along with slight elevations in VEGF, MCP-1 were observed in the blood serum of rapamycin-treated mice. Rapamycin-treated mice exhibited significantly enhanced autophagy and elevated expression of klotho protein, particularly in the kidney. Rapamycin treatment also increased cardiomyocyte Ca2+-sensitivity and enhanced the rate constant of force re-development, which may also contribute to the enhanced survival rate in elderly mice. LA - English DB - MTMT ER - TY - JOUR AU - Gyöngyösi, Alexandra AU - Csáki, Nikolett AU - Pető, Ágota AU - Szőke, Kitti AU - Fenyvesi, Ferenc AU - Bácskay, Ildikó AU - Lekli, István TI - BGP-15 Protects against Doxorubicin-Induced Cell Toxicity via Enhanced Mitochondrial Function JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 6 PG - 13 SN - 1661-6596 DO - 10.3390/ijms24065269 UR - https://m2.mtmt.hu/api/publication/33691053 ID - 33691053 AB - Doxorubicin (DOX) is an efficacious and commonly used chemotherapeutic agent. However, its clinical use is limited due to dose-dependent cardiotoxicity. Several mechanisms have been proposed to play a role in DOX-induced cardiotoxicity, such as free radical generation, oxidative stress, mitochondrial dysfunction, altered apoptosis, and autophagy dysregulation. BGP-15 has a wide range of cytoprotective effects, including mitochondrial protection, but up to now, there is no information about any of its beneficial effects on DOX-induced cardiotoxicity. In this study, we investigated whether the protective effects of BGP-15 pretreatment are predominantly via preserving mitochondrial function, reducing mitochondrial ROS production, and if it has an influence on autophagy processes. H9c2 cardiomyocytes were pretreated with 50 mu M of BGP-15 prior to different concentrations (0.1; 1; 3 mu M) of DOX exposure. We found that BGP-15 pretreatment significantly improved the cell viability after 12 and 24 h DOX exposure. BGP-15 ameliorated lactate dehydrogenase (LDH) release and cell apoptosis induced by DOX. Additionally, BGP-15 pretreatment attenuated the level of mitochondrial oxidative stress and the loss of mitochondrial membrane potential. Moreover, BGP-15 further slightly modulated the autophagic flux, which was measurably decreased by DOX treatment. Hence, our findings clearly revealed that BGP-15 might be a promising agent for alleviating the cardiotoxicity of DOX. This critical mechanism appears to be given by the protective effect of BGP-15 on mitochondria. LA - English DB - MTMT ER - TY - JOUR AU - Józsa, Liza AU - Vasvári, Gábor AU - Sinka, Dávid AU - Nemes, Dániel AU - Ujhelyi, Zoltán AU - Vecsernyés, Miklós AU - Váradi, Judit AU - Fenyvesi, Ferenc AU - Lekli, István AU - Gyöngyösi, Alexandra AU - Bácskay, Ildikó AU - Siposné Fehér, Pálma TI - Enhanced Antioxidant and Anti-Inflammatory Effects of Self-Nano and Microemulsifying Drug Delivery Systems Containing Curcumin JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 19 PG - 22 SN - 1420-3049 DO - 10.3390/molecules27196652 UR - https://m2.mtmt.hu/api/publication/33135106 ID - 33135106 AB - 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 results of the MTT cytotoxicity assay on human keratinocyte cells (HaCaT) and colorectal adenocarcinoma cells (Caco-2) showed that the curcumin-containing preparations were non-cytotoxic at 5 w/v%. According to the results of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide dismutase (SOD) assays, SNEDDS showed significantly higher antioxidant activity. The anti-inflammatory effect of the SN/MEDDS was screened by enzyme-linked immunosorbent assay (ELISA). SNEDDS formulated with Labrasol as surfactant, reduced tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels below 60% at a concentration of 10 w/w%. Our results verified the promising use of SN/MEDDS for the delivery of curcumin. This study demonstrates that the SN/MEDDS could be promising alternatives for the formulation of poorly soluble lipophilic compounds with low bioavailability. LA - English DB - MTMT ER - TY - JOUR AU - Csépányi, Evelin AU - Gyöngyösi, Alexandra AU - Lekli, István AU - Tósaki, Árpád AU - Bak, István TI - Beta-Carotene Affects the Effects of Heme Oxygenase-1 in Isolated, Ischemic/Reperfused Rat Hearts: Potential Role of the Iron JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 9 PG - 12 SN - 1420-3049 DO - 10.3390/molecules27093039 UR - https://m2.mtmt.hu/api/publication/32814186 ID - 32814186 N1 - Export Date: 7 September 2022 LA - English DB - MTMT ER - TY - JOUR AU - Pető, Ágota AU - Kósa, Dóra AU - Haimhoffer, Ádám AU - Siposné Fehér, Pálma AU - Ujhelyi, Zoltán AU - Sinka, Dávid AU - Fenyvesi, Ferenc AU - Váradi, Judit AU - Vecsernyés, Miklós AU - Gyöngyösi, Alexandra AU - Lekli, István AU - Szentesi, Péter AU - Marton, Annamária AU - Gombos, Imre AU - Dukic, Barbara AU - Vigh, László AU - Bácskay, Ildikó TI - Nicotinic Amidoxime Derivate BGP-15, Topical Dosage Formulation and Anti-Inflammatory Effect JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 13 PY - 2021 IS - 12 PG - 17 SN - 1999-4923 DO - 10.3390/pharmaceutics13122037 UR - https://m2.mtmt.hu/api/publication/32515212 ID - 32515212 AB - BGP-15 is a Hungarian-developed drug candidate with numerous beneficial effects. Its potential anti-inflammatory effect is a common assumption, but it has not been investigated in topical formulations yet. The aim of our study was to formulate 10% BGP-15 creams with different penetration enhancers to ensure good drug delivery, improve bioavailability of the drug and investigate the potential anti-inflammatory effect of BGP-15 creams in vivo. Since the exact mechanism of the effect is still unknown, the antioxidant effect (tested with UVB radiation) and the ability of BGP-15 to decrease macrophage activation were evaluated. Biocompatibility investigations were carried out on HaCaT cells to make sure that the formulations and the selected excipients can be safely used. Dosage form studies were also completed with texture analysis and in vitro release with Franz diffusion chamber apparatus. Our results show that the ointments were able to reduce the extent of local inflammation in mice, but the exact mechanism of the effect remains unknown since BGP-15 did not show any antioxidant effect, nor was it able to decrease LPS-induced macrophage activation. Our results support the hypothesis that BGP-15 has a potential anti-inflammatory effect, even if it is topically applied, but the mechanism of the effect remains unclear and requires further pharmacological studies. LA - English DB - MTMT ER - TY - JOUR AU - Haimhoffer, Ádám AU - Fenyvesi, Ferenc AU - Lekli, István AU - Béresová, Monika AU - Bak, István AU - Czagány, Máté AU - Vasvári, Gábor AU - Bácskay, Ildikó AU - Tóth, Judit AU - Budai, István TI - Preparation of Acyclovir-Containing Solid Foam by Ultrasonic Batch Technology JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 13 PY - 2021 IS - 10 PG - 15 SN - 1999-4923 DO - 10.3390/pharmaceutics13101571 UR - https://m2.mtmt.hu/api/publication/32246883 ID - 32246883 N1 - 322037 LA - English DB - MTMT ER -