@article{MTMT:35738710, title = {Evaluation of Permeability, Safety, and Stability of Nanosized Ketoprofen Co-Spray-Dried with Mannitol for Carrier-Free Pulmonary Systems}, url = {https://m2.mtmt.hu/api/publication/35738710}, author = {Banat, Heba Fayez Mahmoud and Gróf, Ilona and Deli, Mária Anna and Ambrus, Rita and Pannonhalminé Csóka, Ildikó}, doi = {10.3390/app15031547}, journal-iso = {APPL SCI-BASEL}, journal = {APPLIED SCIENCES-BASEL}, volume = {15}, unique-id = {35738710}, abstract = {Pulmonary drug delivery presents a promising approach for managing respiratory diseases, enabling localized drug deposition and minimizing systemic side effects. Building upon previous research, this study investigates the cytotoxicity, permeability, and stability of a novel carrier-free dry powder inhaler (DPI) formulation comprising nanosized ketoprofen (KTP) and mannitol (MNT). The formulation was prepared using wet media milling to produce KTP-nanosuspensions, followed by spray drying to achieve combined powders suitable for inhalation. Cell viability and permeability were conducted in both alveolar (A549) and bronchial (CFBE) models. Stability was assessed after storage in hydroxypropyl methylcellulose (HPMC) capsules under stress conditions (40 °C, 75% RH), as per ICH guidelines. KTP showed good penetration through both models, with lower permeability through the CFBE barrier. The MNT-containing sample (F1) increased permeability by 1.4-fold in A549. All formulations had no effect on cell barrier integrity or viability after the impedance test, confirming their safety. During stability assessment, the particle size remained consistent, and the partially amorphous state of KTP was retained over time. However, moisture absorption induced surface roughening and partial agglomeration, leading to reduced fine particle fraction (FPF) and emitted fraction (EF). Despite these changes, the mass median aerodynamic diameter (MMAD) remained stable, confirming the formulation’s continued applicability for pulmonary delivery. Future research should focus on optimizing excipient content, alternative capsule materials, and storage conditions to mitigate moisture-related issues. Hence, the findings demonstrate that the developed ketoprofen–mannitol DPI retains its quality and performance characteristics over an extended period, making it a viable option for pulmonary drug delivery.}, year = {2025}, eissn = {2076-3417}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524; Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781} } @article{MTMT:35772795, title = {Alanine and glutathione targeting of dopamine- or ibuprofen-coupled polypeptide nanocarriers increases both crossing and protective effects on a blood–brain barrier model}, url = {https://m2.mtmt.hu/api/publication/35772795}, author = {Mészáros, Mária and Phan, Thi Ha My and Vigh, Judit Piroska and Porkoláb, Gergő and Kocsis, Anna and Szecskó, Anikó and Páli, Emese Kincső and Cser, Nárcisz Mónika and Polgár, Tamás Ferenc and Kecskeméti, Gábor and Walter, Fruzsina and Schwamborn, Jens C. and Janáky, Tamás and Jan, Jeng-Shiung and Veszelka, Szilvia and Deli, Mária Anna}, doi = {10.1186/s12987-025-00623-2}, journal-iso = {FLUIDS BARRIERS CNS}, journal = {FLUIDS AND BARRIERS OF THE CNS}, volume = {22}, unique-id = {35772795}, issn = {2045-8118}, abstract = {Targeting the blood–brain barrier (BBB) is a key step for effective brain delivery of nanocarriers. We have previously discovered that combinations of BBB nutrient transporter ligands alanine and glutathione (A-GSH), increase the permeability of vesicular and polypeptide nanocarriers containing model cargo across the BBB. Our aim was to investigate dopamine- and ibuprofen-coupled 3-armed poly(l-glutamic acid) nanocarriers targeted by A-GSH for transfer across a novel human co-culture model with induced BBB properties. In addition, the protective effect of ibuprofen containing nanoparticles on cytokine-induced barrier damage was also measured.}, year = {2025}, eissn = {2045-8118}, orcid-numbers = {Kecskeméti, Gábor/0000-0002-5584-6869; Walter, Fruzsina/0000-0001-8145-2823; Janáky, Tamás/0000-0002-6466-8283; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:35780823, title = {Much More than Nutrients: The Protective Effects of Nutraceuticals on the Blood–Brain Barrier in Diseases}, url = {https://m2.mtmt.hu/api/publication/35780823}, author = {Kocsis, Anna and Kucsápszky, Nóra and Santa Maria, Anaraquel and Hunyadi, Attila and Deli, Mária Anna and Walter, Fruzsina}, doi = {10.3390/nu17050766}, journal-iso = {NUTRIENTS}, journal = {NUTRIENTS}, volume = {17}, unique-id = {35780823}, abstract = {The dysfunction of the blood–brain barrier (BBB) is well described in several diseases, and is considered a pathological factor in many neurological disorders. This review summarizes the most important groups of natural compounds, including alkaloids, flavonoids, anthocyanidines, carotenoids, lipids, and vitamins that were investigated for their potential protective effects on brain endothelium. The brain penetration of these compounds and their interaction with BBB efflux transporters and solute carriers are discussed. The cerebrovascular endothelium is considered a therapeutic target for natural compounds in diseases. In preclinical studies modeling systemic and central nervous system diseases, nutraceuticals exerted beneficial effects on the BBB. In vivo, they decreased BBB permeability, brain edema, astrocyte swelling, and morphological changes in the vessel structure and basal lamina. At the level of brain endothelial cells, nutraceuticals increased cell survival and decreased apoptosis. From the general endothelial functions, decreased angiogenesis and increased levels of vasodilating agents were demonstrated. From the BBB functions, elevated barrier integrity by tightened intercellular junctions, and increased expression and activity of BBB transporters, such as efflux pumps, solute carriers, and metabolic enzymes, were shown. Nutraceuticals enhanced the antioxidative defense and exerted anti-inflammatory effects at the BBB. The most important signaling changes mediating the increased cell survival and BBB stability were the activation of the WNT, PI3K-AKT, and NRF2 pathways, and inhibition of the MAPK, JNK, ERK, and NF-κB pathways. Nutraceuticals represent a valuable source of new potentially therapeutic molecules to treat brain diseases by protecting the BBB.}, year = {2025}, eissn = {2072-6643}, orcid-numbers = {Santa Maria, Anaraquel/0000-0003-3505-5477; Hunyadi, Attila/0000-0003-0074-3472; Deli, Mária Anna/0000-0001-6084-6524; Walter, Fruzsina/0000-0001-8145-2823} } @CONFERENCE{MTMT:35780856, title = {Characterization of a new human stem cell based blood-brain barrier and brain organoid lab-on-a-chip model}, url = {https://m2.mtmt.hu/api/publication/35780856}, author = {Kocsis, Anna and Vigh, Judit Piroska and Santa Maria, Anaraquel and Nóra, Kucsápszky and Silvia, Bolognin and Jens, C. Schwamborn and Kincses, András and Szecskó, Anikó and Veszelka, Szilvia and Mészáros, Mária and Dér, András and Deli, Mária Anna and Walter, Fruzsina}, booktitle = {Annual Meeting of the Hungarian Neuroscience Society, MITT 2025, Abstract Book}, unique-id = {35780856}, year = {2025}, pages = {118-118}, orcid-numbers = {Santa Maria, Anaraquel/0000-0003-3505-5477; Deli, Mária Anna/0000-0001-6084-6524; Walter, Fruzsina/0000-0001-8145-2823} } @article{MTMT:36070164, title = {PepH3-modified nanocarriers for delivery of therapeutics across the blood-brain barrier}, url = {https://m2.mtmt.hu/api/publication/36070164}, author = {Szecskó, Anikó and Mészáros, Mária and Simões, Beatriz and Cavaco, Marco and Chaparro, Catarina and Porkoláb, Gergő and Castanho, Miguel A.R.B. and Deli, Mária Anna and Neves, Vera and Veszelka, Szilvia}, doi = {10.1186/s12987-025-00641-0}, journal-iso = {FLUIDS BARRIERS CNS}, journal = {FLUIDS AND BARRIERS OF THE CNS}, volume = {22}, unique-id = {36070164}, issn = {2045-8118}, year = {2025}, eissn = {2045-8118}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:36072118, title = {Nicotinamide derivatives protect the blood-brain barrier against oxidative stress.}, url = {https://m2.mtmt.hu/api/publication/36072118}, author = {Zandona, Antonio and Szecskó, Anikó and Žunec, Suzana and Jovanović, Ivana Novak and Bušić, Valentina and Sokač, Dajana Gašo and Deli, Mária Anna and Katalinić, Maja and Veszelka, Szilvia}, doi = {10.1016/j.biopha.2025.118018}, journal-iso = {BIOMED PHARMACOTHER}, journal = {BIOMEDICINE & PHARMACOTHERAPY}, volume = {186}, unique-id = {36072118}, issn = {0753-3322}, abstract = {Nicotinamides play a crucial role in energy metabolism and maintenance of the redox homeostasis counteracting oxidative stress and elevated reactive oxidative species (ROS) in human cells. The levels of nicotinamides decline with age and are associated with various pathologies, including ones linked with the blood-brain barrier disorder. Therefore, the investigation of the bioactivity of synthetic nicotinamide derivates (NAs) and evaluation of their potential to protect the blood-brain barrier (BBB) from oxidative stress is emerging as an important new strategy. In the current study, we tested different NAs as potential exogenous substitutes for such biological processes. All tested derivatives were non-toxic and attenuated elevation of ROS production in brain endothelial cells induced by tert-butyl hydroperoxide (tBHP), but one specifically was protective on the cell-cultured model of the BBB. The most promising NA was a derivative containing methoxy moiety (NA-4OCH3), which not only increased cell impedance, but had a protective effect on brain endothelial cells barrier against tBHP-induced oxidative stress on several levels: reducing the ROS level and restoring the activity of glutathione, mitochondrial membrane potential, superoxide dismutase enzymes activity to the basal level. In addition, NA-4OCH3 increased the integrity of both human and rat cell-based BBB model after tBHP-treatment seen by the elevated transendothelial electrical resistance, tight junction protein claudin-5 level as well as the decreased permeability of markers across the barrier. This study highlights novel approach to protect the BBB from oxidative stress-induced dysfunction, positioning NA-4OCH3 as potential neuroprotective agent for ROS-mediated disease interventions, with implications for neurodegeneration and BBB.}, keywords = {Blood-Brain Barrier; Reactive oxidative species; Brain endothelial cells; Oxidative stress; Nicotinamide derivates}, year = {2025}, eissn = {1950-6007}, orcid-numbers = {Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:36116321, title = {Mannitol-leucine synergy in nanocrystal agglomerates for enhanced systemic delivery of inhaled ketoprofen: Pharmacokinetics and safety in ovalbumin-sensitized rats}, url = {https://m2.mtmt.hu/api/publication/36116321}, author = {Banat, Heba Fayez Mahmoud and Pannonhalminé Csóka, Ildikó and Kun-Szabó, Fruzsina and Fodor, Gergely and Somogyi, Petra and Peták, Ferenc and Party, Petra and Sztojkov-Ivanov, Anita and Ducza, Eszter and Berkecz, Róbert and Gróf, Ilona and Deli, Mária Anna and Ambrus, Rita}, doi = {10.1016/j.ijpharm.2025.125610}, journal-iso = {INT J PHARM}, journal = {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, volume = {676}, unique-id = {36116321}, issn = {0378-5173}, abstract = {Pulmonary administration offers a promising needle-free approach for systemic delivery of nonsteroidal anti-inflammatory drugs (NSAIDs), improving bioavailability and reducing required doses. While mannitol and leucine are widely used in inhalation formulations, their potential to enhance systemic drug delivery via the pulmonary route remains largely unexplored. This study utilizes the nanocrystal agglomerates (NCAs) approach to develop an inhalable NSAID formulation, with ketoprofen (KTP) as a model drug. Wet media milling and nano spray drying were employed for NCA fabrication, and the roles of mannitol and leucine were evaluated individually and in combination. Notably, their combination exhibited synergy, overcoming limitations observed with individual excipients. Mannitol-based sample (K1M) reduced aerosol performance by increasing the mass median aerodynamic diameter (MMAD) to 4.5 mu m, whereas leucine-based sample (K1L) improved aerosolization but resulted in a low MMAD (<1 m), suggesting a high tendency for exhalation. The combined mannitol-leucine formulation (K1ML) achieved optimal aerosol performance, balancing dispersibility and controlled deposition. K1ML also exhibited the fastest drug release (99 % in 5 min) and enhanced permeability across the alveolar barrier while maintaining biocompatibility. Pharmacokinetic analysis confirmed that inhaled K1ML provided superior bioavailability (AUC 73 mu g.h/mL) compared to oral KTP nanosuspension (42 mu g.h/mL) and raw KTP (9 mu g.h/mL). Nonetheless, prolonged inhalation in asthmatic models (ovalbumin-sensitised rats) impaired pulmonary function, emphasizing the need for dose optimization. These findings demonstrate that the mannitol-leucine combination in NCAs enhances systemic NSAID delivery, optimizing both aerosol performance and bioavailability. Future studies should refine dosing strategies to ensure long-term safety and clinical feasibility.}, year = {2025}, eissn = {1873-3476}, orcid-numbers = {Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781; Fodor, Gergely/0000-0002-4736-4966; Peták, Ferenc/0000-0001-6249-9327; Berkecz, Róbert/0000-0002-9076-2177; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:36131445, title = {Investigation of blood–brain barrier penetration and pharmacokinetics of a new formulation of cyanide antidote dimethyl trisulfide}, url = {https://m2.mtmt.hu/api/publication/36131445}, author = {Kiss, Lóránd and Walter, Fruzsina and Katona, Gábor and Santa Maria, Anaraquel and Whiteman, Ashley C. and Rios, Christian T. and Kelley, Kyler D. and Nelson, Breanna and Thompson, David E. and Pannonhalminé Csóka, Ildikó and Révész, Piroska and Deli, Mária Anna and Petrikovics, Ilona}, doi = {10.1007/s13530-025-00257-9}, journal-iso = {Toxicology Environmental Health Sci}, journal = {TOXICOLOGY AND ENVIRONMENTAL HEALTH SCIENCES}, volume = {17}, unique-id = {36131445}, issn = {2005-9752}, year = {2025}, eissn = {2233-7784}, pages = {313-323}, orcid-numbers = {Walter, Fruzsina/0000-0001-8145-2823; Katona, Gábor/0000-0003-1564-4813; Santa Maria, Anaraquel/0000-0003-3505-5477; Pannonhalminé Csóka, Ildikó/0000-0003-0807-2781; Révész, Piroska/0000-0002-5336-6052; Deli, Mária Anna/0000-0001-6084-6524} } @article{MTMT:36150231, title = {The impact of the novel sigma1 receptor ligand (S)-L1 on brain endothelial cells and cerebrovascular reactivity challenged by ischemia}, url = {https://m2.mtmt.hu/api/publication/36150231}, author = {Kecskés, Szilvia and Mészáros, Mária and Dvorácskó, Szabolcs and Szabó, Írisz and Porkoláb, Gergő and Barna, Lilla and Harazin, András and Szecskó, Anikó and Menyhárt, Ákos and Bari, Ferenc and Deli, Mária Anna and Penke, Botond and Farkas, Eszter and Veszelka, Szilvia}, doi = {10.1016/j.ejphar.2025.177724}, journal-iso = {EUR J PHARMACOL}, journal = {EUROPEAN JOURNAL OF PHARMACOLOGY}, volume = {1000}, unique-id = {36150231}, issn = {0014-2999}, abstract = {Intracellular sigma-1 receptors (sigma1 receptors) have a versatile function through the regulation of lipid rafts, neuroreceptors and ion channels, and can influence signal transduction and neuronal plasticity. Since decreased activity of sigma1 receptors is a common pathological feature in the early stages of many neurological diseases, sigma1 receptor agonists may represent a promising therapeutic tool for the treatment of these disorders. In this study, we aimed to comprehensively investigate the potential protective effects of the novel synthetic sigma1 receptor agonist (S)-L1 against endothelial endoplasmic reticulum (ER) stress and cerebral ischemia. In binding affinity experiments, we showed that (S)-L1 has a high affinity and selectivity for sigma1 receptor with virtually no affinity for any of the other receptors tested. Next, (S)-L1 exerted protection against endoplasmic reticulum stress in human brain endothelial cells, consistent with the localization of sigma1 receptor in endothelial cells. Furthermore, (S)-L1 penetration was demonstrated across the cell culture model of the blood-brain barrier, providing a rationale for neuronal action in addition to endothelial protection. Finally, (S)-L1 inhibited spreading depolarization, suppressed apoptosis and rescued astrocytes in a rat model of cerebral ischemia. Based on our results, (S)-L1 exerts a protective effect on both brain endothelial cells and neural tissue. Moreover, since these experiments revealed no affinity for serotonergic receptors, the compound holds promise as an adjuvant therapy for the treatment of cerebrovascular disease without potential psychedelic side effects. Copyright © 2025. Published by Elsevier B.V.}, keywords = {Blood-Brain Barrier; Cerebral ischemia; Neurovascular coupling; Brain endothelial cells; sigma-1 receptor ligand}, year = {2025}, eissn = {1879-0712}, orcid-numbers = {Harazin, András/0000-0002-0904-5606; Menyhárt, Ákos/0000-0002-1355-3208; Bari, Ferenc/0000-0001-9383-452X; Deli, Mária Anna/0000-0001-6084-6524; Penke, Botond/0000-0003-0938-0567; Farkas, Eszter/0000-0002-8478-9664} } @misc{MTMT:36161130, title = {LABEL-FREE BIOPHYSICAL TOOLS FOR CELLULAR ADHESION, BIOMECHANICS, AND SINGLE-CELL INJECTION}, url = {https://m2.mtmt.hu/api/publication/36161130}, author = {Horváth, Róbert and Porkoláb, Gergő and Magyaródi, Beatrix and Rajmon, Imola and Kovács, Kinga Dóra and Kanyó, Nicolett and Varga, Dános Sebestyén and Walter, Fruzsina and Martins, Ana and Péter, Beatrix and Székács, Inna and Dér, András and Deli, Mária Anna}, unique-id = {36161130}, year = {2025}, orcid-numbers = {Horváth, Róbert/0000-0001-8617-2302; Walter, Fruzsina/0000-0001-8145-2823; Martins, Ana/0000-0002-8541-7440; Deli, Mária Anna/0000-0001-6084-6524} }