TY - JOUR
AU - Banat, Heba Fayez Mahmoud
AU - Gróf, Ilona
AU - Deli, Mária Anna
AU - Ambrus, Rita
AU - Pannonhalminé Csóka, Ildikó
TI - Evaluation of Permeability, Safety, and Stability of Nanosized Ketoprofen Co-Spray-Dried with Mannitol for Carrier-Free Pulmonary Systems
JF - APPLIED SCIENCES-BASEL
J2 - APPL SCI-BASEL
VL - 15
PY - 2025
IS - 3
PG - 19
SN - 2076-3417
DO - 10.3390/app15031547
UR - https://m2.mtmt.hu/api/publication/35738710
ID - 35738710
N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office; [NKFIH_OTKA K_146148]
Funding text: This research was supported by National Research, Development and Innovation Office, NKFIH_OTKA K_146148.
AB - 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.
LA - English
DB - MTMT
ER -
TY - JOUR
AU - Mészáros, Mária
AU - Phan, Thi Ha My
AU - Vigh, Judit Piroska
AU - Porkoláb, Gergő
AU - Kocsis, Anna
AU - Szecskó, Anikó
AU - Páli, Emese Kincső
AU - Cser, Nárcisz Mónika
AU - Polgár, Tamás Ferenc
AU - Kecskeméti, Gábor
AU - Walter, Fruzsina
AU - Schwamborn, Jens C.
AU - Janáky, Tamás
AU - Jan, Jeng-Shiung
AU - Veszelka, Szilvia
AU - Deli, Mária Anna
TI - Alanine and glutathione targeting of dopamine- or ibuprofen-coupled polypeptide nanocarriers increases both crossing and protective effects on a blood–brain barrier model
JF - FLUIDS AND BARRIERS OF THE CNS
J2 - FLUIDS BARRIERS CNS
VL - 22
PY - 2025
IS - 1
PG - 23
SN - 2045-8118
DO - 10.1186/s12987-025-00623-2
UR - https://m2.mtmt.hu/api/publication/35772795
ID - 35772795
N1 - Funding Agency and Grant Number: HUN-REN Biological Research Centre, Szeged; National Research, Development and Innovation Office of Hungary [NNE-29617, K143766]; National Research, Development and Innovation Office, Budapest, Hungary [PD 138930]; Gedeon Richter Plc. Centenarial Foundation; New National Excellence Program of the Ministry for Innovation and Technology [UNKP-23-3-SZTE-535]; National Academy of Scientist Education Program of the National Biomedical Foundation under the Hungarian Ministry of Culture and Innovation; New National Excellence Program [UNKP-23-3-SZTE-315]; Egyetemi Kutatoi Osztondij Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund [EKOP-393]; Hungarian Research Network [SA-111/2021]; National ScienceTechnology Council, Taiwan [NSTC107-2923-M-006-002-MY3]; Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund [143233]
Funding text: Open access funding provided by HUN-REN Biological Research Centre, Szeged. This work was funded by the National Research, Development and Innovation Office of Hungary, grant numbers NNE-29617 (M-ERA.NET2 nanoPD) and K143766 (for M.A.D.). 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). J.P.V. was supported by the New National Excellence Program of the Ministry for Innovation and Technology (UNKP-23-3-SZTE-535). G.P. was supported by the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation. E.K.P. was supported by the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation. T.F.P. was supported by the UNKP-23-3-SZTE-315 New National Excellence Program and the EKOP-393 Egyetemi Kutatoi Osztondij Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund. F.R.W. was supported by the grant SA-111/2021 from the Hungarian Research Network. J.S.J. was supported by the National ScienceTechnology Council, Taiwan: NSTC107-2923-M-006-002-MY3 (M-ERA.NET2 nanoPD). S.V. was supported by the project no.143233, which has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the FK_22 funding scheme.
AB - 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.
LA - English
DB - MTMT
ER -
TY - JOUR
AU - Kocsis, Anna
AU - Kucsápszky, Nóra
AU - Santa Maria, Anaraquel
AU - Hunyadi, Attila
AU - Deli, Mária Anna
AU - Walter, Fruzsina
TI - Much More than Nutrients: The Protective Effects of Nutraceuticals on the Blood–Brain Barrier in Diseases
JF - NUTRIENTS
J2 - NUTRIENTS
VL - 17
PY - 2025
IS - 5
PG - 45
SN - 2072-6643
DO - 10.3390/nu17050766
UR - https://m2.mtmt.hu/api/publication/35780823
ID - 35780823
N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [2022-1.2.6-TET-IPARI-TR-2022-00024]; Hungarian Research Network [SA-111/2021]
Funding text: This work was funded by grant 2022-1.2.6-TET-IPARI-TR-2022-00024 (D.M.A. and A.H.) from the National Research, Development and Innovation Office of Hungary. F.R.W. was funded by the Hungarian Research Network grant number SA-111/2021.
AB - 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.
LA - English
DB - MTMT
ER -
TY - CONF
AU - Kocsis, Anna
AU - Vigh, Judit Piroska
AU - Santa Maria, Anaraquel
AU - Nóra, Kucsápszky
AU - Silvia, Bolognin
AU - Jens, C. Schwamborn
AU - Kincses, András
AU - Szecskó, Anikó
AU - Veszelka, Szilvia
AU - Mészáros, Mária
AU - Dér, András
AU - Deli, Mária Anna
AU - Walter, Fruzsina
TI - Characterization of a new human stem cell based blood-brain barrier and brain organoid lab-on-a-chip model
T2 - Annual Meeting of the Hungarian Neuroscience Society, MITT 2025, Abstract Book
PY - 2025
SP - 118
EP - 118
PG - 1
UR - https://m2.mtmt.hu/api/publication/35780856
ID - 35780856
LA - English
DB - MTMT
ER -
TY - JOUR
AU - Szecskó, Anikó
AU - Mészáros, Mária
AU - Simões, Beatriz
AU - Cavaco, Marco
AU - Chaparro, Catarina
AU - Porkoláb, Gergő
AU - Castanho, Miguel A.R.B.
AU - Deli, Mária Anna
AU - Neves, Vera
AU - Veszelka, Szilvia
TI - PepH3-modified nanocarriers for delivery of therapeutics across the blood-brain barrier
JF - FLUIDS AND BARRIERS OF THE CNS
J2 - FLUIDS BARRIERS CNS
VL - 22
PY - 2025
IS - 1
PG - 19
SN - 2045-8118
DO - 10.1186/s12987-025-00641-0
UR - https://m2.mtmt.hu/api/publication/36070164
ID - 36070164
LA - English
DB - MTMT
ER -
TY - JOUR
AU - Zandona, Antonio
AU - Szecskó, Anikó
AU - Žunec, Suzana
AU - Jovanović, Ivana Novak
AU - Bušić, Valentina
AU - Sokač, Dajana Gašo
AU - Deli, Mária Anna
AU - Katalinić, Maja
AU - Veszelka, Szilvia
TI - Nicotinamide derivatives protect the blood-brain barrier against oxidative stress.
JF - BIOMEDICINE & PHARMACOTHERAPY
J2 - BIOMED PHARMACOTHER
VL - 186
PY - 2025
PG - 12
SN - 0753-3322
DO - 10.1016/j.biopha.2025.118018
UR - https://m2.mtmt.hu/api/publication/36072118
ID - 36072118
AB - 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.
LA - English
DB - MTMT
ER -
TY - JOUR
AU - Banat, Heba Fayez Mahmoud
AU - Pannonhalminé Csóka, Ildikó
AU - Kun-Szabó, Fruzsina
AU - Fodor, Gergely
AU - Somogyi, Petra
AU - Peták, Ferenc
AU - Party, Petra
AU - Sztojkov-Ivanov, Anita
AU - Ducza, Eszter
AU - Berkecz, Róbert
AU - Gróf, Ilona
AU - Deli, Mária Anna
AU - Ambrus, Rita
TI - Mannitol-leucine synergy in nanocrystal agglomerates for enhanced systemic delivery of inhaled ketoprofen: Pharmacokinetics and safety in ovalbumin-sensitized rats
JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS
J2 - INT J PHARM
VL - 676
PY - 2025
PG - 18
SN - 0378-5173
DO - 10.1016/j.ijpharm.2025.125610
UR - https://m2.mtmt.hu/api/publication/36116321
ID - 36116321
N1 - Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös u.6, Szeged, H-6720, Hungary
Department of Medical Physics and Informatics, Albert Szent-Györgyi Medical School, University of Szeged, Korányi fasor 9, Szeged, Hungary
Institute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, Szeged, H-6720, Hungary
Institute of Pharmaceutical Analysis, Faculty of Pharmacy, University of Szeged Somogyi, u. 4., Szeged, Hungary
Department of Forensic Medicine, Albert Szent-Györgyi Health Centre, Kossuth Lajos sgt. 40., Szeged, Hungary
Institute of Biophysics, HUN-REN Biological Research Centre, Temesvári Blvd. 62, Szeged, H-6726, Hungary
Export Date: 06 May 2025; Cited By: 0; Correspondence Address: R. Ambrus; Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged, Eötvös u.6, H-6720, Hungary; email: ambrus.rita@szte.hu; CODEN: IJPHD
AB - 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.
LA - English
DB - MTMT
ER -
TY - JOUR
AU - Kiss, Lóránd
AU - Walter, Fruzsina
AU - Katona, Gábor
AU - Santa Maria, Anaraquel
AU - Whiteman, Ashley C.
AU - Rios, Christian T.
AU - Kelley, Kyler D.
AU - Nelson, Breanna
AU - Thompson, David E.
AU - Pannonhalminé Csóka, Ildikó
AU - Révész, Piroska
AU - Deli, Mária Anna
AU - Petrikovics, Ilona
TI - Investigation of blood–brain barrier penetration and pharmacokinetics of a new formulation of cyanide antidote dimethyl trisulfide
JF - TOXICOLOGY AND ENVIRONMENTAL HEALTH SCIENCES
J2 - Toxicology Environmental Health Sci
VL - 17
PY - 2025
IS - 2
SP - 313
EP - 323
PG - 11
SN - 2005-9752
DO - 10.1007/s13530-025-00257-9
UR - https://m2.mtmt.hu/api/publication/36131445
ID - 36131445
N1 - Helyreigazítás a közleményhez 36244884 rekordban, DOI: 10.1007/s13530-025-00266-8 (BSzÁ, SZTE admin5, 2025-08-27)
LA - English
DB - MTMT
ER -
TY - JOUR
AU - Kecskés, Szilvia
AU - Mészáros, Mária
AU - Dvorácskó, Szabolcs
AU - Szabó, Írisz
AU - Porkoláb, Gergő
AU - Barna, Lilla
AU - Harazin, András
AU - Szecskó, Anikó
AU - Menyhárt, Ákos
AU - Bari, Ferenc
AU - Deli, Mária Anna
AU - Penke, Botond
AU - Farkas, Eszter
AU - Veszelka, Szilvia
TI - The impact of the novel sigma1 receptor ligand (S)-L1 on brain endothelial cells and cerebrovascular reactivity challenged by ischemia
JF - EUROPEAN JOURNAL OF PHARMACOLOGY
J2 - EUR J PHARMACOL
VL - 1000
PY - 2025
PG - 10
SN - 0014-2999
DO - 10.1016/j.ejphar.2025.177724
UR - https://m2.mtmt.hu/api/publication/36150231
ID - 36150231
N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [PD139012, FK143233, K146725]; EU's Horizon 2020 research and innovation program [739593]; Ministry of Innovation and Technology of Hungary; National Research, Development and Innovation Fund [TKP2021-EGA-28, TKP2021-EGA]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences; [GINOP-2.3.2-15-2016-00060]; [K134334]
Funding text: This work was supported by the National Research, Development and Innovation Office of Hungary, (grant numbers GINOP-2.3.2-15-2016-00060, K134334, PD139012, FK143233, K146725) ; The EU's Horizon 2020 research and innovation program grant number 739593; the Ministry of Innovation and Technology of Hungary and the National Research, Development and Innovation Fund (grant number TKP2021-EGA-28 financed under the TKP2021-EGA funding scheme) , and the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences.
AB - 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.
LA - English
DB - MTMT
ER -
TY - GEN
AU - Horváth, Róbert
AU - Porkoláb, Gergő
AU - Magyaródi, Beatrix
AU - Rajmon, Imola
AU - Kovács, Kinga Dóra
AU - Kanyó, Nicolett
AU - Varga, Dános Sebestyén
AU - Walter, Fruzsina
AU - Martins, Ana
AU - Péter, Beatrix
AU - Székács, Inna
AU - Dér, András
AU - Deli, Mária Anna
TI - LABEL-FREE BIOPHYSICAL TOOLS FOR CELLULAR ADHESION, BIOMECHANICS, AND SINGLE-CELL INJECTION
PY - 2025
UR - https://m2.mtmt.hu/api/publication/36161130
ID - 36161130
LA - English
DB - MTMT
ER -