TY - JOUR AU - Hassan, Alharith A. A. AU - Sovány, Tamás AU - Pamlényi, Krisztián AU - Deák, Martin AU - Varga, Viktória AU - Csapó, Edit AU - Regdon, Géza (ifj.) AU - Pannonhalminé Csóka, Ildikó AU - Kristó, Katalin TI - QbD Approach-Based Preparation and Optimization of Hydrophobic Ion-Pairing Complex of Lysozyme with Sodium Dodecyl Sulphate to Enhance Stability in Lipid-Based Carriers JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 16 PY - 2024 IS - 5 SP - 589 SN - 1999-4923 DO - 10.3390/pharmaceutics16050589 UR - https://m2.mtmt.hu/api/publication/34832111 ID - 34832111 AB - Hydrophobic ion pairing (HIP) complexation was found to be an efficient approach in modulating the release and enhancing the stability and encapsulation of hydrophilic macromolecules such as proteins in hydrophobic nano/microcarriers. The present work strives to develop and optimize the preparation of the HIP complex of the antimicrobial enzyme lysozyme (LYZ) with the ion-pairing agent (IPA) sodium dodecyl sulphate (SDS) relying on the quality-by-design (QbD) approach. The quality target product profile (QTPP) includes the achievement of maximal lipophilicity in a reversible manner to enable the maintenance of biological activity. The related critical quality attributes (CQAs) were defined as complexation efficacy, complex stability, enzyme recovery and activity. Three risk assessment (RA) tools were used to identify and rank the critical process parameters (CPPs) and critical material attributes (CMAs). From this assessment, the pH of the medium, LYZ:SDS molar ratio and drying conditions were determined as high-risk factors that need to be investigated. To the best of our knowledge, for the first time, electrostatic titration was used as a smart approach to determine the optimum molar ratio at different pH values. Based on the predefined CQAs, pH 8 with an LYZ/SDS molar ratio of 1:8 was found to be the optimal condition for complexation efficiency and recovery (%) of a biologically active enzyme. A cost-effective drying process based on a ventilated oven was developed, which resulted in complex qualities comparable to those obtained by the commonly used freeze-drying method. In a nutshell, the optimum conditions for the preparation of the LYZ/SDS HIP complex were efficiently facilitated by the rational application of QbD principles and the utilization of efficient electrostatic titration and ventilated oven-drying methods. LA - English DB - MTMT ER - TY - JOUR AU - Tanács, Dániel AU - Berkecz, Róbert AU - Bozsó, Zsolt AU - Tóth, Gábor AU - Armstrong, Daniel W. AU - Péter, Antal AU - Ilisz, István TI - Liquid Chromatographic Enantioseparation of Newly Synthesized Fluorinated Tryptophan Analogs Applying Macrocyclic Glycopeptides-Based Chiral Stationary Phases Utilizing Core-Shell Particles JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 9 PG - 16 SN - 1661-6596 DO - 10.3390/ijms25094719 UR - https://m2.mtmt.hu/api/publication/34830921 ID - 34830921 AB - Due to the favorable features obtained through the incorporation of fluorine atom(s), fluorinated drugs are a group with emerging pharmaceutical importance. As their commercial availability is still very limited, to expand the range of possible candidates, new fluorinated tryptophan analogs were synthesized. Control of enantiopurity during the synthesis procedure requires that highly efficient enantioseparation methods be available. In this work, the enantioseparation of seven fluorinated tryptophans and tryptophan was studied and compared systematically to (i) develop analytical methods for enantioselective separations and (ii) explore the chromatographic features of the fluorotrytophans. For enantioresolution, macrocyclic glycopeptide-based selectors linked to core-shell particles were utilized, applying liquid chromatography-based methods. Application of the polar-ionic mode resulted in asymmetric and broadened peaks, while reversed-phase conditions, together with mobile-phase additives, resulted in baseline separation for all studied fluorinated tryptophans. The marked differences observed between the methanol and acetonitrile-containing eluent systems can be explained by the different solvation abilities of the bulk solvents of the applied mobile phases. Among the studied chiral selectors, teicoplanin and teicoplanin aglycone were found to work effectively. Under optimized conditions, baseline separations were achieved within 6 min. Ionic interactions were semi-quantitatively characterized and found to not influence enantiorecognition. Interestingly, fluorination of the analytes does not lead to marked changes in the chromatographic characteristics of the methanol-containing eluents, while larger differences were noticed when the polar but aprotic acetonitrile was applied. Experiments conducted on the influence of the separation temperature indicated that the separations are enthalpically driven, with only one exception. Enantiomeric elution order was found to be constant on both teicoplanin and teicoplanin aglycone-based chiral stationary phases (L < D) under all applied chromatographic conditions. LA - English DB - MTMT ER - TY - JOUR AU - Party, Petra AU - Sümegi, Sándor Soma AU - Ambrus, Rita TI - Preparation and Investigation of a Nanosized Piroxicam Containing Orodispersible Lyophilizate JF - MICROMACHINES J2 - MICROMACHINES-BASEL VL - 15 PY - 2024 IS - 4 SP - 532 SN - 2072-666X DO - 10.3390/mi15040532 UR - https://m2.mtmt.hu/api/publication/34830531 ID - 34830531 AB - Non-steroidal anti-inflammatory piroxicam (PRX) is a poorly water-soluble drug that provides relief in different arthritides. Reducing the particle size of PRX increases its bioavailability. For pediatric, geriatric, and dysphagic patients, oral dispersible systems ease administration. Moreover, fast disintegration followed by drug release and absorption through the oral mucosa can induce rapid systemic effects. We aimed to produce an orodispersible lyophilizate (OL) consisting of nanosized PRX. PRX was solved in ethyl acetate and then sonicated into a poloxamer-188 solution to perform spray-ultrasound-assisted solvent diffusion-based nanoprecipitation. The solid form was formulated via freeze drying in blister sockets. Mannitol and sodium alginate were applied as excipients. Dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) were used to determine the particle size. The morphology was characterized by scanning electron microscopy (SEM). To establish the crystallinity, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used. A disintegration and in vitro dissolution test were performed. DLS and NTA presented a nanosized PRX diameter. The SEM pictures showed a porous structure. PRX became amorphous according to the XRPD and DSC curves. The disintegration time was less than 1 min and the dissolution profile improved. The final product was an innovative anti-inflammatory drug delivery system. LA - English DB - MTMT ER - TY - JOUR AU - Csatordai, Márta AU - Benkő, Ria AU - Matuz, Mária AU - Engi, Zsófia AU - Csupor, Dezső AU - Lengyel, Csaba Attila AU - Doró, Péter TI - Trends and regional differences in antidiabetic medication use: a nationwide retrospective observational study JF - DIABETOLOGY AND METABOLIC SYNDROME J2 - DIABETOL METAB SYNDR VL - 16 PY - 2024 IS - 1 PG - 10 SN - 1758-5996 DO - 10.1186/s13098-024-01334-8 UR - https://m2.mtmt.hu/api/publication/34824725 ID - 34824725 N1 - Faculty of Pharmacy, Institute of Clinical Pharmacy, University of Szeged, Szikra utca 8, Szeged, 6725, Hungary Albert Szent-Györgyi Health Centre, Central Pharmacy, University of Szeged, Szeged, Hungary Albert Szent-Györgyi Health Centre, Department of Internal Medicine, University of Szeged, Szeged, Hungary Export Date: 3 May 2024 Correspondence Address: Doró, P.; Faculty of Pharmacy, Szikra utca 8, Hungary; email: doro.peter@szte.hu LA - English DB - MTMT ER - TY - JOUR AU - Mészáros, Rebeka Ildikó AU - Szabó, Vivien AU - Kutus, Bence AU - Baán, Kornélia AU - Kónya, Zoltán AU - Kukovecz, Ákos AU - Sipos, Pál Miklós AU - Szabados, Márton TI - Continuous-flow hydrogenation of cinnamaldehyde over catalysts derived from modified CoAl4 layered double hydroxides incorporating Mn, Ni, Cu and Zn ions JF - APPLIED CATALYSIS A-GENERAL J2 - APPL CATAL A-GEN VL - 679 PY - 2024 PG - 14 SN - 0926-860X DO - 10.1016/j.apcata.2024.119738 UR - https://m2.mtmt.hu/api/publication/34801853 ID - 34801853 LA - English DB - MTMT ER - TY - JOUR AU - Bahar, Muhammad Akbar AU - Kusuma, Ikhwan Yuda AU - Visnyovszki, Ádám AU - Matuz, Mária AU - Benkő, Ria AU - Ferenci, Tamás AU - Szabó, Bálint Gergely AU - Hajdú, Edit AU - Pető, Zoltán AU - Csupor, Dezső TI - Favipiravir does not improve viral clearance in mild to moderate COVID-19 – a systematic review and meta-analysis of randomized controlled trials JF - HELIYON J2 - HELIYON VL - 10 PY - 2024 IS - 9 PG - 15 SN - 2405-8440 DO - 10.1016/j.heliyon.2024.e29808 UR - https://m2.mtmt.hu/api/publication/34796471 ID - 34796471 LA - English DB - MTMT ER - TY - JOUR AU - Mardikasari, Sandra Aulia AU - Katona, Gábor AU - Sipos, Bence AU - Pannonhalminé Csóka, Ildikó TI - Essential considerations towards development of effective nasal antibiotic formulation: features, strategies, and future directions JF - EXPERT OPINION ON DRUG DELIVERY J2 - EXPERT OPIN DRUG DELIV PY - 2024 SP - 1 EP - 15 PG - 15 SN - 1742-5247 DO - 10.1080/17425247.2024.2341184 UR - https://m2.mtmt.hu/api/publication/34791444 ID - 34791444 LA - English DB - MTMT ER - TY - JOUR AU - Dewi, Ni Made Amelia Ratnata AU - Benkő, Ria AU - Engi, Zsófia AU - Csupor, Dezső AU - Viola, Réka AU - Csatordai, Márta AU - Matuz, Mária TI - Pain management: opioid use in hospitals JF - EUROPEAN JOURNAL OF HOSPITAL PHARMACY-SCIENCE AND PRACTICE J2 - EUR J HOSP PHARM SCI PRACT VL - 31 PY - 2024 IS - S1 SP - A242 EP - A243 PG - 1 SN - 2047-9956 DO - 10.1136/ejhpharm-2024-eahp.501 UR - https://m2.mtmt.hu/api/publication/34791311 ID - 34791311 LA - English DB - MTMT ER - TY - JOUR AU - Háznagy, Márton Benedek AU - Csámpai, Antal AU - Ugrai, Imre AU - Barnabás, Molnár AU - Matti, Haukka AU - Szakonyi, Zsolt TI - Stereoselective Synthesis and Catalytical Application of Perillaldehyde-Based 3-Amino-1,2-diol Regioisomers JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 8 PG - 25 SN - 1661-6596 DO - 10.3390/ijms25084325 UR - https://m2.mtmt.hu/api/publication/34791082 ID - 34791082 AB - A library of regioisomeric monoterpene-based aminodiols was synthesised and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The synthesis of the first type of aminodiols was achieved starting from (−)-8,9-dihydroperillaldehyde via reductive amination, followed by Boc protection and dihydroxylation with the OsO4/NMO system. Separation of formed stereoisomers resulted in a library of aminodiol diastereoisomers. The library of regioisomeric analogues was obtained starting from (−)-8,9-dihydroperillic alcohol, which was transformed into a mixture of allylic trichloroacetamides via Overman rearrangement. Changing the protecting group to a Boc function, the protected enamines were subjected to dihydroxylation with the OsO4/NMO system, leading to a 71:16:13 mixture of diastereoisomers, which were separated, affording the three isomers in isolated form. The obtained primary aminodiols were transformed into secondary derivatives. The regioselectivity of the ring closure of the N-benzyl-substituted aminodiols with formaldehyde was also investigated, resulting in 1,3-oxazines in an exclusive manner. To explain the stability difference between diastereoisomeric 1,3-oxazines, a series of comparative theoretical modelling studies was carried out. The obtained potential catalysts were applied in the reaction of aromatic aldehydes and diethylzinc with moderate to good enantioselectivities (up to 94% ee), whereas the opposite chiral selectivity was observed between secondary aminodiols and their ring-closed 1,3-oxazine analogues. LA - English DB - MTMT ER - TY - JOUR AU - Bózsity-Faragó, Noémi AU - Nagy, Viktória AU - Szabó, Johanna AU - Pálházi, Balázs AU - Kele, Zoltán AU - Resch, Vivien Erzsébet AU - Paragi, Gábor AU - Zupkó, István AU - Minorics, Renáta AU - Mernyák, Erzsébet TI - Synthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 8 PG - 15 SN - 1661-6596 DO - 10.3390/ijms25084274 UR - https://m2.mtmt.hu/api/publication/34789041 ID - 34789041 AB - Directed structural modifications of natural products offer excellent opportunities to develop selectively acting drug candidates. Natural product hybrids represent a particular compound group. The components of hybrids constructed from different molecular entities may result in synergic action with diminished side effects. Steroidal homo- or heterodimers deserve special attention owing to their potentially high anticancer effect. Inspired by our recently described antiproliferative core-modified estrone derivatives, here, we combined them into heterodimers via Cu(I)-catalyzed azide–alkyne cycloaddition reactions. The two trans-16-azido-3-(O-benzyl)-17-hydroxy-13α-estrone derivatives were reacted with 3-O-propargyl-D-secoestrone alcohol or oxime. The antiproliferative activities of the four newly synthesized dimers were evaluated against a panel of human adherent gynecological cancer cell lines (cervical: Hela, SiHa, C33A; breast: MCF-7, T47D, MDA-MB-231, MDA-MB-361; ovarian: A2780). One heterodimer (12) exerted substantial antiproliferative activity against all investigated cell lines in the submicromolar or low micromolar range. A pronounced proapoptotic effect was observed by fluorescent double staining and flow cytometry on three cervical cell lines. Additionally, cell cycle blockade in the G2/M phase was detected, which might be a consequence of the effect of the dimer on tubulin polymerization. Computational calculations on the taxoid binding site of tubulin revealed potential binding of both steroidal building blocks, mainly with hydrophobic interactions and water bridges. LA - English DB - MTMT ER -