TY - JOUR AU - Rusznyák, Ágnes AU - Szászné Réti-Nagy, Katalin AU - Váradi, Judit AU - Bácskay, Ildikó AU - Vecsernyés, Miklós AU - Fenyvesi, Ferenc TI - Hidroxi-propil-béta-ciklodextrin celluláris internalizációjának és lizoszómákra gyakorolt hatásának vizsgálata JF - EGÉSZSÉGÜGYI INNOVÁCIÓS SZEMLE J2 - EÜ INNOV SZLE VL - 2 PY - 2023 IS - 2 SP - 57 EP - 64 PG - 8 SN - 2939-6026 DO - 10.56626/egis.v2i2.12924 UR - https://m2.mtmt.hu/api/publication/34688027 ID - 34688027 AB - A ciklodextrinek széles körben alkalmazott segédanyagok a lipofil gyógyszerek vízoldhatóságának és biológiai hasznosíthatóságának növelésére. Kutatócsoportunk korábban kimutatta, hogy a ciklodextrinek endocitózissal képesek bejutni a Caco-2 intesztinális epitél sejtekbe, azonban a különböző sejtek esetén történő celluláris internalizációt és az intracelluláris hatásait eddig még nem vizsgálták. Mindemellett a 2-hidroxi-propil-béta-ciklodextrin (HPBCD) koleszterin komplexáló tulajdonságának köszönhetően a C típusú Niemann Pick szindróma kezelésére alkalmazott molekula. Munkánk célja a HPBCD celluláris internalizációjának és a sejtekben található lizoszómákra gyakorolt hatásának vizsgálata és összehasonlítása Caco-2 intesztinális epitél, HeLa méhnyak epitél és hCMEC/D3 agyi endotél sejteken. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Gutayné Tóth, Zsuzsanna AU - Gellén, Gabriella AU - Doan, Minh AU - Eliason, James F. AU - Vincze, János AU - Szente, Lajos AU - Fenyvesi, Ferenc AU - Kormosné, Goda Katalin AU - Vecsernyés, Miklós AU - Szabó, Gábor AU - Bacsó, Zsolt TI - Cholesterol-Depletion-Induced Membrane Repair Carries a Raft Conformer of P-Glycoprotein to the Cell Surface, Indicating Enhanced Cholesterol Trafficking in MDR Cells, Which Makes Them Resistant to Cholesterol Modifications JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 15 PG - 23 SN - 1661-6596 DO - 10.3390/ijms241512335 UR - https://m2.mtmt.hu/api/publication/34086081 ID - 34086081 N1 - Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen, 4032, Hungary MTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Department of Analytical Chemistry, Institute of Chemistry, ELTE Eötvös Loránd University, Budapest, 1053, Hungary Great Lakes Stem Cell Innovation Center, Detroit, MI 48202, United States Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary CycloLab Cyclodextrin Research & Development Laboratory, Ltd, Budapest, 1097, Hungary Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Debrecen, 4032, Hungary Export Date: 15 September 2023 Correspondence Address: Bacso, Z.; Department of Biophysics and Cell Biology, Hungary; email: bacso@med.unideb.hu AB - The human P-glycoprotein (P-gp), a transporter responsible for multidrug resistance, is present in the plasma membrane’s raft and non-raft domains. One specific conformation of P-gp that binds to the monoclonal antibody UIC2 is primarily associated with raft domains and displays heightened internalization in cells overexpressing P-gp, such as in NIH-3T3 MDR1 cells. Our primary objective was to investigate whether the trafficking of this particular P-gp conformer is dependent on cholesterol levels. Surprisingly, depleting cholesterol using cyclodextrin resulted in an unexpected increase in the proportion of raft-associated P-gp within the cell membrane, as determined by UIC2-reactive P-gp. This increase appears to be a compensatory response to cholesterol loss from the plasma membrane, whereby cholesterol-rich raft micro-domains are delivered to the cell surface through an augmented exocytosis process. Furthermore, this exocytotic event is found to be part of a complex trafficking mechanism involving lysosomal exocytosis, which contributes to membrane repair after cholesterol reduction induced by cyclodextrin treatment. Notably, cells overexpressing P-gp demonstrated higher total cellular cholesterol levels, an increased abundance of stable lysosomes, and more effective membrane repair following cholesterol modifications. These modifications encompassed exocytotic events that involved the transport of P-gp-carrying rafts. Importantly, the enhanced membrane repair capability resulted in a durable phenotype for MDR1 expressing cells, as evidenced by significantly improved viabilities of multidrug-resistant Pgp-overexpressing immortal NIH-3T3 MDR1 and MDCK-MDR1 cells compared to their parents when subjected to cholesterol alterations. 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 - Kovács, Renátó AU - Erdélyi, Lóránd AU - Fenyvesi, Ferenc AU - Balla , Noémi AU - Kovács, Fruzsina AU - Vámosi, György AU - Klusóczki, Ágnes AU - Gyöngyösi, Alexandra AU - Bácskay, Ildikó AU - Vecsernyés, Miklós AU - Váradi, Judit TI - Concentration-Dependent Antibacterial Activity of Chitosan on Lactobacillus plantarum JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 1 SN - 1999-4923 DO - 10.3390/pharmaceutics15010018 UR - https://m2.mtmt.hu/api/publication/33434625 ID - 33434625 AB - 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 irreversible interaction and concentration dependence were established in all concentrations. The interaction of fluorescein isothiocyanate (FITC) labeled low molecular weight chitosan and bacterial cells labeled with membrane dye (FM® 4–64) was confirmed by confocal microscopy. In conclusion, the inhibitory effect of chitosan was verified on a probiotic strain, which is an undesirable effect in probiotic preparations containing chitosan additives, while the inhibitory effect experienced with pathogenic strains is beneficial. LA - English DB - MTMT ER - TY - JOUR AU - Veszelka, Szilvia AU - Mészáros, Mária AU - Porkoláb, Gergő AU - Rusznyák, Ágnes AU - Szászné Réti-Nagy, Katalin AU - Deli, Mária Anna AU - Vecsernyés, Miklós AU - Bácskay, Ildikó AU - Váradi, Judit AU - Fenyvesi, Ferenc TI - Effects of Hydroxypropyl-Beta-Cyclodextrin on Cultured Brain Endothelial Cells JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 22 PG - 15 SN - 1420-3049 DO - 10.3390/molecules27227738 UR - https://m2.mtmt.hu/api/publication/33272291 ID - 33272291 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office, Budapest, Hungary [FK124634, NNE-29617, PD 138930]; National Research, Development and Innovation Fund of Hungary under the TKP2021-EGA funding scheme [TKP2021-EGA-18]; European Union and the European Regional Development Fund; National Academy of Scientist Education under Hungarian Ministry of Innovation and Technology [FEIF/646-4/2021-ITM_SZERZ]; StephenW. Kuffler Research Foundation; Gedeon Richter Plc. Centennial Foundation (Hungary); New National Excellence Program of the Ministry for Innovation and Technology from the National Research, Development and Innovation [UNKP-22-3-SZTE-446]; Gedeon Richter Plc. Centenarial Foundation (Hungary); Ministry of Human Resources [NTP-NFTO-22-B-0150]; National Talent Program; Premium Postdoctoral Research Program of the Hungarian Academy of Sciences [Premium-2019-469]; OTKA Young Researcher Excellence Program by the National Research, Development and Innovation Office of Hungary [OTKA-FK 143233]; [GINOP-2.3.4-15-2020-00008] Funding text: This study was supported by FK_17 (FK124634), and NNE-29617 (M-ERA.NET2 nanoPD) research grants of the National Research, Development and Innovation Office, Budapest, Hungary. Project no. TKP2021-EGA-18 was implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme. The work is supported by the GINOP-2.3.4-15-2020-00008 project. The project is co-financed by the European Union and the European Regional Development Fund. G.P. was supported by the National Academy of Scientist Education under the sponsorship of the Hungarian Ministry of Innovation and Technology (FEIF/646-4/2021-ITM_SZERZ), the StephenW. Kuffler Research Foundation and the Gedeon Richter Plc. Centennial Foundation (H-1103 Budapest, Gyomroi str. 19-21. Hungary), as well as by the UNKP-22-3-SZTE-446 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation. M.M. was supported by the research grant (PD 138930) of the National Research, Development and Innovation Office, Budapest, Hungary, the Gedeon Richter Plc. Centenarial Foundation (H-1103 Budapest, Gyomroi str. 19-21. Hungary), and the "National Talent Program" with the financial aid of the Ministry of Human Resources (NTP-NFTO-22-B-0150). S.V. was supported by the Premium Postdoctoral Research Program (Premium-2019-469) of the Hungarian Academy of Sciences, and the OTKA Young Researcher Excellence Program (OTKA-FK 143233) by the National Research, Development and Innovation Office of Hungary. AB - The application of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the treatment of the rare cholesterol and lipid storage disorder Niemann–Pick disease type C opened new perspectives in the development of an efficient therapy. Even if the systemic administration of HPBCD was found to be effective, its low permeability across the blood–brain barrier (BBB) limited the positive neurological effects. Nevertheless, the cellular interactions of HPBCD with brain capillary endothelial cells have not been investigated in detail. In this study, the cytotoxicity, permeability, and cellular internalization of HPBCD on primary rat and immortalized human (hCMEC/D3) brain capillary endothelial cells were investigated. HPBCD shows no cytotoxicity on endothelial cells up to 100 µM, measured by impedance kinetics. Using a fluorescent derivative of HPBCD (FITC-HPBCD) the permeability measurements reveal that on an in vitro triple co-culture BBB model, FITC-HPBCD has low permeability, 0.50 × 10−6 cm/s, while on hCMEC/D3 cell layers, the permeability is higher, 1.86 × 10−5 cm/s. FITC-HPBCD enters brain capillary endothelial cells, is detected in cytoplasmic vesicles and rarely localized in lysosomes. The cellular internalization of HPBCD at the BBB can help to develop new strategies for improved HPBCD effects after systemic administration. 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 - Haimhoffer, Ádám AU - Vas, Alexandra AU - Árvai, Gabriella AU - Jicsinszky, László AU - Fenyvesi, Éva AU - Budai, István AU - Bényei, Attila Csaba AU - Regdon, Géza (ifj.) AU - Rusznyák, Ágnes AU - Vasvári, Gábor AU - Váradi, Judit AU - Bácskay, Ildikó AU - Vecsernyés, Miklós AU - Fenyvesi, Ferenc TI - Investigation of the Drug Carrier Properties of Insoluble Cyclodextrin Polymer Microspheres JF - BIOMOLECULES J2 - BIOMOLECULES VL - 12 PY - 2022 IS - 7 PG - 21 SN - 2218-273X DO - 10.3390/biom12070931 UR - https://m2.mtmt.hu/api/publication/32918236 ID - 32918236 AB - The investigation of the usability of solid insoluble beta-cyclodextrin polymers (beta CDP) 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 beta CDP for drug delivery applications. Solid insoluble cyclodextrin polymer of irregular shape (beta CDPIS) and cyclodextrin microbeads (beta CDPB) 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 mu m, their shape was spherical and surfaces were smooth; while the beta CDPIS particles were around 4 mu m with irregular shape and surface. None of the polymers showed any cytotoxic effect on Caco-2 cells. Both carriers were able to extract curcumin and estradiol from aqueous solutions, and the dissolution test showed prolonged estradiol release. Caco-2 permeability tests were in accordance with the complexation abilities and dissolution of the complexes. This study offers useful data for further pharmaceutical applications of insoluble cyclodextrin polymers. LA - English DB - MTMT ER - TY - JOUR AU - Sinka, Dávid AU - Doma, Enikő AU - Szendi, Nóra AU - Páll, Jázmin AU - Kósa, Dóra AU - Pető, Ágota AU - Siposné Fehér, Pálma AU - Ujhelyi, Zoltán AU - Fenyvesi, Ferenc AU - Váradi, Judit AU - Vecsernyés, Miklós AU - Szűcs, Zsolt AU - Gonda, Sándor AU - Cziáky, Zoltán AU - Kiss, Attila AU - Vasas, Gábor AU - Bácskay, Ildikó TI - Formulation, Characterization and Permeability Studies of Fenugreek (Trigonella foenum-graecum) Containing Self-Emulsifying Drug Delivery System (SEDDS) JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 9 PG - 18 SN - 1420-3049 DO - 10.3390/molecules27092846 UR - https://m2.mtmt.hu/api/publication/32801731 ID - 32801731 AB - Fenugreek is used as a spice and a traditional herbal medicine for a variety of purposes, given its antidiabetic and antioxidant effects. Self-emulsifying drug delivery systems (SEDDS) of herbal drugs are targets of extensive research aiming to increase bioavailability and stability. The study's objective was to formulate SEDDS containing Trigonella foenum-graecum extract to improve the stability of herbal extract and to increase their permeability through a Caco-2 monolayer. A characterized fenugreek dry extract was used for the formulations, while the SEDDS properties were examined by particle size analysis and zeta potential measurements. Permeability assays were carried out on Caco-2 cell monolayers, the integrity of which was monitored by follow-up trans-epithelial electric resistance measurements (TEER). Cytocompatibility was tested by the MTT method, and an indirect dissolution test was performed, using DPPH antioxidant reagent. Two different SEDDS compositions were formulated from a standardized fenugreek dry extract at either the micro- or the nanoemulsion scale with sufficient stability, enhanced bioavailability of the compounds, and sustained release from HPMC capsules. Based on our results, a modern, non-toxic, cytocompatible fenugreek SEDDS formulation with high antioxidant capacity was developed in order to improve the permeability and bioavailability of all components. LA - English DB - MTMT ER - TY - JOUR AU - Pető, Ágota AU - Kósa, Dóra AU - Haimhoffer, Ádám AU - Nemes, Dániel AU - Siposné Fehér, Pálma AU - Ujhelyi, Zoltán AU - Vecsernyés, Miklós AU - Váradi, Judit AU - Fenyvesi, Ferenc AU - Frum, Adina AU - Gligor, Felicia Gabriela AU - Vicaș, Laura Grațiela AU - Marian, Eleonora AU - Jurca, Tunde AU - Pallag, Annamaria AU - Muresan, Mariana Eugenia AU - Tóth, Zoltán AU - Bácskay, Ildikó TI - Topical Dosage Formulation of Lyophilized Philadelphus coronarius L. Leaf and Flower: Antimicrobial, Antioxidant and Anti-Inflammatory Assessment of the Plant JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 9 SN - 1420-3049 DO - 10.3390/molecules27092652 UR - https://m2.mtmt.hu/api/publication/32789179 ID - 32789179 AB - 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 decrease IL-4 production when it was tested on HaCaT cells. P. coronarius is a promising herb, and its topical application in antimicrobial therapy can be a useful addition to modern medical therapy. LA - English DB - MTMT ER - TY - JOUR AU - Erdélyi, Lóránd AU - Fenyvesi, Ferenc AU - Gál, Bernadett AU - Haimhoffer, Ádám AU - Vasvári, Gábor AU - Budai, István AU - Gálné Remenyik, Judit AU - Bakai-Bereczki, Ilona AU - Siposné Fehér, Pálma AU - Ujhelyi, Zoltán AU - Bácskay, Ildikó AU - Vecsernyés, Miklós AU - Kovács, Renátó AU - Váradi, Judit TI - Investigation of the Role and Effectiveness of Chitosan Coating on Probiotic Microcapsules JF - POLYMERS J2 - POLYMERS-BASEL VL - 14 PY - 2022 IS - 9 SP - 1 EP - 16 PG - 16 SN - 2073-4360 DO - 10.3390/polym14091664 UR - https://m2.mtmt.hu/api/publication/32789039 ID - 32789039 LA - English DB - MTMT ER -