{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:16:44Z","timestamp":1792088204397,"version":"4.4.0"},"reference-count":110,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005632","name":"National Centre for Research and Development (NCBR)","doi-asserted-by":"publisher","award":["TANGO-V-A\/0008\/2021-00"],"award-info":[{"award-number":["TANGO-V-A\/0008\/2021-00"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sulfonylureas (SUs)\u2014a class of drugs primarily used to treat type 2 diabetes\u2014have recently attracted interest for their potential anticancer properties. While some studies have explored the chemical modification or design of new SU derivatives, our work instead centers on biological evaluations of all commercially available SUs in combination with doxorubicin (DOXO). These antidiabetic agents act by stimulating insulin secretion via KATP channel inhibition, and because KATP channels share structural features with ATP-binding cassette (ABC) transporters involved in multidrug resistance (e.g., P-glycoprotein, MRP1, and MRP2), SUs may also reduce cancer cell drug efflux. In this study, we systematically examined each commercially available SU for potential synergy with DOXO in a panel of human cancer cell lines. Notably, combining DOXO with glimepiride (GLIM), the newest SU, results in a 4.4-fold increase in cytotoxicity against MCF-7 breast cancer cells relative to DOXO alone. Mechanistic studies suggest that the observed synergy may arise from increased intracellular accumulation of DOXO. Preliminary in vivo experiments support these findings, showing that DOXO (5 mg\/kg, i.v.) plus GLIM (4 mg\/kg, i.p.) is more effective at inhibiting 4T1 tumor growth in mice than DOXO alone. Additionally, we show that adding a small amount of the surfactant Tween-80 to culture media affects SU binding to bovine serum albumin (BSA), potentially unmasking anticancer effects of SUs that strongly bind to proteins. Overall, these results underscore the potential of repurposing existing SUs to enhance standard chemotherapy regimens.<\/jats:p>","DOI":"10.3390\/ijms26041429","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T04:44:03Z","timestamp":1739162643000},"page":"1429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Combining Sulfonylureas with Anticancer Drugs: Evidence of Synergistic Efficacy with Doxorubicin In Vitro and In Vivo"],"prefix":"10.3390","volume":"26","author":[{"given":"Mateusz D.","family":"Tomczyk","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6374-9356","authenticated-orcid":false,"given":"Karolina","family":"Matczak","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of \u0141\u00f3d\u017a, 141\/143, 90-236 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4379-0367","authenticated-orcid":false,"given":"Marta","family":"Denel-Bobrowska","sequence":"additional","affiliation":[{"name":"Screening Laboratory, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0732-6607","authenticated-orcid":false,"given":"Grzegorz","family":"Dzido","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering and Process Design, Silesian University of Technology, Strzody 9, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kubicka","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of \u0141\u00f3d\u017a, 141\/143, 90-236 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Gendosz de Carrillo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical Sciences, Medical University of Silesia, Medyk\u00f3w 18, 40-055 Katowice, Poland"},{"name":"Department of Histology and Cell Pathology, Faculty of Medical Sciences, Medical University of Silesia, Jordana 19, 41-808 Zabrze, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-7080","authenticated-orcid":false,"given":"Tomasz","family":"Cicho\u0144","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sk\u0142odowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-102 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1698-5257","authenticated-orcid":false,"given":"Marlena","family":"Golec","sequence":"additional","affiliation":[{"name":"Department of Radiopharmacy and Preclinical PET Imaging, Maria Sk\u0142odowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-102 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Powieczko","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Rzetelny","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy, Hospital of the Ministry of Interior and Administration in \u0141\u00f3d\u017a, P\u00f3\u0142nocna 42, 91-425 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4628-9017","authenticated-orcid":false,"given":"Agnieszka B.","family":"Olejniczak","sequence":"additional","affiliation":[{"name":"Screening Laboratory, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4468-7898","authenticated-orcid":false,"given":"Horacio","family":"P\u00e9rez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Cat\u00f3lica de Murcia (UCAM), Campus de los Jer\u00f3nimos 135, 30107 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1158\/1535-7163.MCT-09-1186","article-title":"Metformin in Cancer Therapy: A New Perspective for an Old Antidiabetic Drug?","volume":"9","author":"Sahra","year":"2010","journal-title":"Mol. Cancer Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.tips.2018.07.006","article-title":"Metformin as an Anticancer Agent","volume":"39","author":"Vancura","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"FSO410","DOI":"10.2144\/fsoa-2019-0053","article-title":"Anticancer activity of metformin: A systematic review of the literature","volume":"5","author":"Aljofan","year":"2019","journal-title":"Future Sci. OA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2337\/dc06-0922","article-title":"Prospective study of hyperglycemia and cancer risk","volume":"30","author":"Stattin","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/cas.12043","article-title":"Diabetes mellitus and cancer risk: Review of the epidemiological evidence","volume":"104","author":"Shikata","year":"2012","journal-title":"Cancer Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.4093\/dmj.2011.35.3.193","article-title":"Diabetes and Cancer: Is Diabetes Causally Related to Cancer?","volume":"35","author":"Suh","year":"2011","journal-title":"Diabetes Metab. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"276","DOI":"10.2337\/diaspect.27.4.276","article-title":"The Diabetes-Cancer Link","volume":"27","author":"Collins","year":"2014","journal-title":"Diabetes Spectr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"132","DOI":"10.4103\/ijem.IJEM_556_17","article-title":"Consensus recommendations on sulfonylurea and sulfonylurea combinations in the management of type 2 diabetes mellitus\u2014International Task Force","volume":"22","author":"Kalra","year":"2018","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3S","DOI":"10.1016\/0002-9343(90)90330-G","article-title":"Molecular mechanisms of action of glyburide on the beta cell","volume":"89","author":"Aubrey","year":"1990","journal-title":"Am. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/ddr.21640","article-title":"Selected pharmacotherapy agents as antiproliferative and anti-inflammatory compounds","volume":"81","author":"Alkhalil","year":"2020","journal-title":"Drug Dev. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jpba.2018.03.025","article-title":"Unveiling anticancer potential of glibenclamide: Its synergistic cytotoxicity with doxorubicin on cancer cells","volume":"154","author":"Subramaniyam","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"991","DOI":"10.18388\/abp.1999_4124","article-title":"The access of metabolites into yeast mitochondria in the presence and absence of the voltage dependent anion selective channel [YVDAC1]","volume":"46","author":"Kmita","year":"1999","journal-title":"Acta Biochim. Pol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/jcp.1041650121","article-title":"Changes in membrane potential during the progression of MCF-7 human mammary tumor cells through the cell cycle","volume":"165","author":"Wonderlin","year":"1995","journal-title":"J. Cell. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/2050-6511-14-6","article-title":"Glibenclamide inhibits cell growth by inducing G0\/G1 arrest in the human breast cancer cell line MDA-MB-231","volume":"14","author":"Medina","year":"2013","journal-title":"BMC Pharmacol Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0304-3835(02)00348-8","article-title":"Expression and activity of potassium ion channels in human prostate cancer","volume":"186","author":"Abdul","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"842","DOI":"10.3892\/or.2013.2875","article-title":"Voltage-gated and ATP-sensitive K+ channels are associated with cell proliferation and tumorigenesis of human glioma","volume":"31","author":"Ru","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"783","DOI":"10.2147\/OTT.S326614","article-title":"Potassium Channels as a Target for Cancer Therapy: Current Perspectives","volume":"15","author":"Cayo","year":"2022","journal-title":"OncoTargets Ther."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, M., Tian, P., Zhao, Q., Ma, X., and Zhang, Y. (2023). Potassium channels: Novel targets for tumor diagnosis and chemoresistance. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1074469"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"212","DOI":"10.2174\/157489207782497181","article-title":"Potassium Channels are a New Target Field in Anticancer Drug Design","volume":"2","author":"Villalonga","year":"2007","journal-title":"Recent Pat. Anticancer Drug Discov."},{"key":"ref_20","first-page":"261","article-title":"Blockage of voltage-gated K+ channels inhibits adhesion and proliferation of hepatocarcinoma cells","volume":"11","author":"Zhou","year":"2003","journal-title":"Int. J. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"465","DOI":"10.3892\/ijo.2012.1483","article-title":"Depolarization potentiates TRAIL-induced apoptosis in human melanoma cells: Role for ATP-sensitive K+ channels and endoplasmic reticulum stress","volume":"41","author":"Suzuki","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1634\/theoncologist.2013-0177","article-title":"Effects of sulfonylureas on tumor growth: A review of the literature","volume":"18","author":"Pasello","year":"2013","journal-title":"Oncologist"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1007\/s004240050829","article-title":"P-glycoprotein inhibition by glibenclamide and related compounds","volume":"437","author":"Golstein","year":"1999","journal-title":"Pflugers Arch."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/sj.bjp.0703863","article-title":"The sulphonylurea glibenclamide inhibits multidrug resistance protein (MRP1) activity in human lung cancer cells","volume":"132","author":"Payen","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3727\/096504005776404526","article-title":"Effect of glibenclamide on N-nitroso-N-methylurea-induced mammary tumors in diabetic and nondiabetic rats","volume":"15","author":"Cocca","year":"2005","journal-title":"Oncol. Res."},{"key":"ref_26","first-page":"52","article-title":"An in-vitro and in Silico Anticancer Study of FDA Approved Antidiabetic Drugs Glimepiride and Empagliflozin: Life Sciences-Biochemistry for better diagnosis and therapy","volume":"10","author":"Faridi","year":"2022","journal-title":"Int. J. Life Sci. Biotechnol. Pharma Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105128","DOI":"10.1016\/j.tiv.2021.105128","article-title":"A potential role of calpains in sulfonylureas (SUs)-mediated death of human pancreatic cancer cells (1.2B4)","volume":"73","author":"Fleszar","year":"2021","journal-title":"Toxicol. Vitro"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3777","DOI":"10.2147\/OTT.S240252","article-title":"The Anti-Breast Cancer Effect and Mechanism of Glimepiride-Metformin Adduct","volume":"13","author":"Long","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1186\/s13046-021-02077-4","article-title":"Downregulated CLIP3 induces radioresistance by enhancing stemness and glycolytic flux in glioblastoma","volume":"40","author":"Kang","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2651790","DOI":"10.1155\/2022\/2651790","article-title":"The Effects of 6 Common Antidiabetic Drugs on Anti-PD1 Immune Checkpoint Inhibitor in Tumor Treatment","volume":"2022","author":"Zhan","year":"2022","journal-title":"J. Immunol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cairns, L.V., Lappin, K.M., Mutch, A., Ali, A., Matchett, K.B., and Mills, K.I. (2021). Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221810163"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9966","DOI":"10.18632\/oncotarget.2483","article-title":"Glipizide, an antidiabetic drug, suppresses tumor growth and metastasis by inhibiting angiogenesis","volume":"5","author":"Qi","year":"2014","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.yexcr.2015.03.012","article-title":"Glipizide suppresses embryonic vasculogenesis and angiogenesis through targeting natriuretic peptide receptor A","volume":"333","author":"Gu","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1007\/s11033-021-06942-5","article-title":"The effects of glipizide on DNA damage and nuclear transport in differentiated 3T3-L1 adipocytes","volume":"49","author":"Cevik","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.2174\/1871520621666210910085733","article-title":"Glipizide Combined with ANP Suppresses Breast Cancer Growth and Metastasis by Inhibiting Angiogenesis through VEGF\/VEGFR2 Signaling","volume":"22","author":"Mao","year":"2022","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100021","DOI":"10.18632\/oncotarget.21754","article-title":"Glipizide sensitizes lung cancer cells to TRAIL-induced apoptosis via Akt\/mTOR\/autophagy pathways","volume":"8","author":"Nazim","year":"2017","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"172598","DOI":"10.1016\/j.ejphar.2019.172598","article-title":"Sulfonylurea derivatives and cancer, friend or foe?","volume":"861","author":"Hendriks","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1021\/cb300189b","article-title":"Colloidal aggregation affects the efficacy of anticancer drugs in cell culture","volume":"7","author":"Owen","year":"2012","journal-title":"ACS Chem. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/10837450802498894","article-title":"Co-solvent solubilization of some poorly-soluble antidiabetic drugs","volume":"14","author":"Seedher","year":"2009","journal-title":"Pharm. Dev. Technol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1080\/03639045.2018.1431656","article-title":"Impact of various solid carriers and spray drying on pre\/post compression properties of solid SNEDDS loaded with glimepiride: In vitro-ex vivo evaluation and cytotoxicity assessment","volume":"44","author":"Rajesh","year":"2018","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"19968","DOI":"10.1021\/acsomega.0c01228","article-title":"Physicochemical Characterization, Molecular Docking, and In Vitro Dissolution of Glimepiride-Captisol Inclusion Complexes","volume":"32","author":"Pal","year":"2020","journal-title":"ACS Omega"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1345\/aph.1C397","article-title":"Glimepiride Pharmacokinetics in Obese Versus Non-Obese Diabetic Patients","volume":"38","author":"Shukla","year":"2004","journal-title":"Ann. Pharmacother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1515\/DMDI.1994.11.4.331","article-title":"Absolute bioavailability of glimepiride (Amaryl) after oral administration","volume":"11","author":"Badian","year":"1994","journal-title":"Drug Metabol. Drug Interact."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1365-2710.2006.00766.x","article-title":"Pharmacokinetic and pharmacodynamic modelling of the effects of glimepiride on insulin secretion and glucose lowering in healthy humans","volume":"31","author":"Yun","year":"2006","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jchromb.2018.10.015","article-title":"Binding studies based on ultrafast affinity extraction and single- or two-column systems: Interactions of second- and third-generation sulfonylurea drugs with normal or glycated human serum albumin","volume":"1102\u20131103","author":"Yang","year":"2018","journal-title":"J. Chromatogr. B"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ejps.2004.05.008","article-title":"Improvement of gliquidone hypoglycaemic effect in rats by cyclodextrin formulations","volume":"23","author":"Miro","year":"2004","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1039\/C8CE01848K","article-title":"Preparation and characterization for multicomponent crystals of the antidiabetic drug gliquidone based on crystal engineering","volume":"21","author":"Jia","year":"2019","journal-title":"CrystEngComm"},{"key":"ref_48","first-page":"1933","article-title":"Pharmakokinetisches Verhalten von Gliquidone (AR-DF 26), einem neuen Sulfonylharnstoff (Zusammenfassung der bisherigen Untersuchungen) [Pharmacokinetic behaviour of gliquidone (AR-DF 26), a new sulfonyl urea. Summary of the studies so far (author\u2019s transl)]","volume":"25","author":"Kopitar","year":"1975","journal-title":"Arzneimittelforschung"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1039\/C5CE02402A","article-title":"Novel cocrystals of gliclazide: Characterization and evaluation","volume":"18","author":"Chadha","year":"2016","journal-title":"CrystEngComm"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1021\/acs.cgd.6b01804","article-title":"Salts and Cocrystals of the Antidiabetic Drugs Gliclazide, Tolbutamide, an Glipizide: Solubility Enhancements through Drug\u2013Coformer Interactions","volume":"17","author":"Samie","year":"2017","journal-title":"Cryst. Growth Des."},{"key":"ref_51","first-page":"49","article-title":"Solubility Enhancement of Gliclazide via Co-crystallization with Malonic Acid","volume":"16","author":"Ibrahim","year":"2019","journal-title":"Life Sci. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1046\/j.1365-2125.2000.00162.x","article-title":"Pharmacokinetics and pharmacodynamics of gliclazide in Caucasians and Australian Aborigines with type 2 diabetes","volume":"49","author":"Davis","year":"2000","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0168-8227(91)90005-X","article-title":"The mode of action and clinical pharmacology of gliclazide: A review","volume":"14","author":"Campbell","year":"1991","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.chroma.2014.10.092","article-title":"Analysis of free drug fractions by ultrafast affinity extraction: Interactions of sulfonylurea drugs with normal or glycated human serum albumin","volume":"1371","author":"Zheng","year":"2014","journal-title":"J. Chromatogr. A"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Poddar, S., Woolfork, A.G., Iftekhar, S., Ovbude, S.T., and Hage, D.S. (2023). Characterization of binding by sulfonylureas with normal or modified human serum albumin using affinity microcolumns prepared by entrapment. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 1226.","DOI":"10.1016\/j.jchromb.2023.123798"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1021\/acs.cgd.7b00933","article-title":"Crystal Engineering: A Remedy to Tailor the Biopharmaceutical Aspects of Glibenclamide","volume":"18","author":"Goya","year":"2018","journal-title":"Cryst. Growth Des."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.0954-6820.1980.tb01199.x","article-title":"Comparative Single-Dose Kinetics and Effects of Four Sulfonylureas in Healthy Volunteers","volume":"208","author":"Sartor","year":"1980","journal-title":"Acta Med. Scand."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1177\/106002809603000507","article-title":"Pharmacokinetics and Pharmacodynamics of Glyburide in Young and Elderly Patients with Non-Insulin-Dependent Diabetes Mellitus","volume":"30","author":"Jaber","year":"1996","journal-title":"Ann. Pharmacother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0378-5173(87)90107-4","article-title":"Comparison of pharmacokinetics and pharmacodynamics of a conventional and a new rapidly dissolving glibenclamide preparation","volume":"38","author":"Shaheen","year":"1987","journal-title":"Int. J. Pharm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1002\/open.202100246","article-title":"Solubility Enhancement of Antidiabetic Drugs Using a Co-Crystallization Approach","volume":"10","author":"Batisai","year":"2021","journal-title":"ChemistryOpen"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1208\/s12249-017-0727-z","article-title":"Stable Co-Crystals of Glipizide with Enhanced Dissolution Profiles: Preparation and Characterization","volume":"18","author":"Pandey","year":"2017","journal-title":"AAPS PharmSciTech"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/j.1552-4604.1989.tb03289.x","article-title":"Glipizide Pharmacokinetics: Effects of Age, Diabetes, and Multiple Dosing","volume":"29","author":"Kradjan","year":"1989","journal-title":"J. Clin. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/BF00315518","article-title":"The pharmacokinetics and pharmacodynamics of 12 weeks of glyburide therapy in obese diabetics","volume":"45","author":"Jaber","year":"1993","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_64","unstructured":"Yalkowsky, S.H., and Dannenfelser, R.M. (1992). The AQUASOL dATAbASE of Aqueous Solubility, University of Arizona, College of Pharmacy. [5th ed.]."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1001\/jama.1956.02960500015005","article-title":"Clinical experiences with carbutamide, an orally given hypoglycemic agent; preliminary report","volume":"160","author":"Ridolfo","year":"1956","journal-title":"JAMA"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Sarragu\u00e7a, M.C., Ribeiro, P.R.S., Nunes, C., and Seabra, C.L. (2022). Solids Turn into Liquids\u2014Liquid Eutectic Systems of Pharmaceutics to Improve Drug Solubility. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030279"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.3109\/03639048709068694","article-title":"Dissolution of Chlorpropamide Tablets in A Methanol-Water Binary Solvent System","volume":"13","author":"Dodge","year":"1987","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1007\/s11095-013-1278-y","article-title":"A Novel Method for Determining the Solubility of Small Molecules in Aqueous Media and Polymer Solvent Systems Using Solution Calorimetry","volume":"31","author":"Fadda","year":"2014","journal-title":"Pharm. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1002\/cpt1972135part1710","article-title":"Pharmacokinetics and biotransformation of chlorpropamide in man","volume":"13","author":"Taylor","year":"1972","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1021\/cg050049m","article-title":"Amphiphilic Block Copolymer as a Crystal Habit Modifier","volume":"5","author":"Kuldipkumar","year":"2005","journal-title":"Cryst. Growth Des."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/jps.2600711119","article-title":"Bioavailability of tolazamide from tablets: Comparison of in vitro and in vivo results","volume":"71","author":"Welling","year":"1982","journal-title":"J. Pharm. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Proks, P., Kramer, H., Haythorne, E., and Ashcroft, F.M. (2018). Binding of sulphonylureas to plasma proteins\u2014A KATP channel perspective. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197634"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jlumin.2018.01.017","article-title":"Spectroscopic and molecular docking study to understand the binding interaction of rosiglitazone with bovine serum albumin in presence of valsartan","volume":"197","author":"Pawar","year":"2018","journal-title":"J. Lumin."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s10867-014-9367-7","article-title":"Determination of the second virial coefficient of bovine serum albumin under varying pH and ionic strength by composition-gradient multi-angle static light scattering","volume":"41","author":"Ma","year":"2015","journal-title":"J. Biol. Phys."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3114","DOI":"10.1021\/acsomega.2c06447","article-title":"Interaction of Ibuprofen with Partially Unfolded Bovine Serum Albumin in the Presence of Ionic Micelles and Oligosaccharides at Different \u03bbex and pH: A Spectroscopic Analysis","volume":"8","author":"Rout","year":"2023","journal-title":"ACS Omega"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/BF02278643","article-title":"Qualitative study of the competition of drugs in binding to serum albumin","volume":"37","author":"Sun","year":"1993","journal-title":"Chromatographia"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1080\/01932691.2021.1997759","article-title":"Investigation of mechanistic interactions between Rifampicin and bovine serum albumin in the presence of different surfactants","volume":"44","author":"Shingada","year":"2021","journal-title":"J. Dispers. Sci. Technol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s002800050859","article-title":"Effect of Tween-80 on cell killing by etoposide in human lung adenocarcinoma cells","volume":"43","author":"Tsujino","year":"1999","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"17685","DOI":"10.1039\/D3RA02883F","article-title":"A recent overview of surfactant\u2013drug interactions and their importance","volume":"13","author":"Pokhrel","year":"2023","journal-title":"RSC Adv."},{"key":"ref_80","first-page":"11","article-title":"Solubility Enhancement of Drugs with Aid of Surfactants: Research Done Since Last Two Decades","volume":"5","author":"Jwalapuram","year":"2020","journal-title":"Int. J. Life Sci. Biotechnol. Pharma Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1248\/bpb.b13-00898","article-title":"Improvement of the Antitumor Activity of Poorly Soluble Sapacitabine (CS-682) by Using Soluplus\u00ae as a Surfactant","volume":"37","author":"Obata","year":"2014","journal-title":"Biol. Pharm. Bull."},{"key":"ref_82","first-page":"3005","article-title":"Comparison of effects of surfactants with other MDR reversing agents on intracellular uptake of epirubicin in Caco-2 cell line","volume":"18","author":"Lo","year":"1998","journal-title":"Anticancer Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1080\/10826070802225585","article-title":"Characterization of Mass Ionizable Degradation Products of Gliclazide by LC\/ESI-MS","volume":"31","author":"Bansal","year":"2008","journal-title":"J. Liq. Chromatogr. Relat."},{"key":"ref_84","first-page":"17","article-title":"Studies on the in vitro phototoxicity of the antidiabetes drug glipizide","volume":"13","author":"Vargas","year":"2000","journal-title":"In Vitr. Mol. Toxicol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1080\/10428190802353591","article-title":"Preclinical versus clinical drug combination studies","volume":"49","author":"Chou","year":"2008","journal-title":"Leuk. Lymphoma."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/S0006-2952(01)00796-1","article-title":"Induction of G(2)\/M phase arrest and apoptosis by a new synthetic anti-cancer agent, DW2282, in promyelocytic leukemia (HL-60) cells","volume":"62","author":"Piao","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_87","first-page":"710","article-title":"The Standardization of Hemoglobin Measurement","volume":"217","author":"Drabkin","year":"1949","journal-title":"Am. J. Med. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1016\/j.bbamem.2010.05.010","article-title":"Erythrocyte morphological states, phases, transitions and trajectories","volume":"1798","author":"Rudenko","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_89","first-page":"132","article-title":"The Effect of Cryoprotective Agents on Proteins of the Erythrocyte Membrane-Cytoskeleton Complex","volume":"15","author":"Zemlianskykh","year":"2021","journal-title":"Biochem. (Mosc.) Suppl. B Biomed. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/2211-5463.12193","article-title":"Toxic effects of dimethyl sulfoxide on red blood cells, platelets, and vascular endothelial cells in vitro","volume":"7","author":"Yi","year":"2017","journal-title":"FEBS Open Bio"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/jps.2600550704","article-title":"Hemolysis of erythrocytes by antibacterial preservatives III: Influence of dimethyl sulfoxide on the hemolytic activity of phenol","volume":"55","author":"Ansel","year":"1966","journal-title":"J. Pharm. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s00249-021-01527-3","article-title":"The effects of incubation media on the assessment of the shape of human erythrocytes by flow cytometry: A contribution to mathematical data interpretation to enable wider application of the method","volume":"50","author":"Drvenica","year":"2021","journal-title":"Eur. Biophys. J."},{"key":"ref_93","first-page":"6331","article-title":"Combination of glycosphingosomes and liposomal doxorubicin shows increased activity against dimethyl-\u03b1-benzanthracene-induced fibrosarcoma in mice","volume":"2015","author":"Khan","year":"2015","journal-title":"Int. J. Nanotechnol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s11095-019-2677-5","article-title":"Nano-Co-Delivery of Berberine and Anticancer Drug Using PLGA Nanoparticles: Exploration of Better Anticancer Activity and In Vivo Kinetics","volume":"36","author":"Khan","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1046\/j.1365-2141.1996.275810.x","article-title":"Glyburide-induced acute haemolysis in a G6PD-deficient patient with NIDDM","volume":"92","author":"Meloni","year":"1996","journal-title":"Br. J. Haematol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/ajh.2830230313","article-title":"The mechanisms of sulfonylurea-induced immune hemolysis: Case report and review of the literature","volume":"23","author":"Kopicky","year":"1986","journal-title":"Am. J. Hematol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"904","DOI":"10.2337\/diacare.13.8.904a","article-title":"Relationship of Maternal and Fetal Outcome to Glucose Tolerance During Pregnancy in Whites and Indian Asians","volume":"13","author":"Burden","year":"1990","journal-title":"Diabetes Care"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1136\/bmj.1.5802.728","article-title":"Haemolytic anaemia associated with antibodies to tolbutamide and phenacetin","volume":"1","author":"Bird","year":"1972","journal-title":"Br. Med. J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1463-1326.2004.00305.x","article-title":"Comparison of the effects of glimepiride and glibenclamide on adipose tissue tumour necrosis factor-\u03b1 mRNA expression and cellularity","volume":"6","author":"Mori","year":"2003","journal-title":"Diabetes Obes. Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/fcp.12434","article-title":"Glimepiride prevents paraquat-induced Parkinsonism in mice: Involvement of oxidative stress and neuroinflammation","volume":"33","author":"Ishola","year":"2018","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1021\/js980302n","article-title":"Synthesis, stability, and pharmacological evaluation of nipecotic acid prodrugs","volume":"88","author":"Bonina","year":"1999","journal-title":"J. Pharm. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4168","DOI":"10.1016\/j.bmc.2005.04.042","article-title":"Towards new boron carriers for boron neutron capture therapy: Metallacarboranes and their nucleoside conjugates","volume":"13","author":"Lesnikowski","year":"2005","journal-title":"Bioorg. Med. Chem."},{"key":"ref_103","unstructured":"Chou, T.C., and Martin, N. (2005). CompuSyn for Drug Combinations: PC Software and User\u2019s Guide: A Computer Program for Quantitation of Synergism and Antagonism in Drug Combinations, and the Determination of IC50 and ED50 and LD50 Values, ComboSyn."},{"key":"ref_104","first-page":"432","article-title":"Fluorescence-Based Assays for Measuring Doxorubicin in Biological Systems","volume":"2","author":"Kauffman","year":"2016","journal-title":"React. Oxyg. Species"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"96","DOI":"10.2478\/s11532-008-0080-x","article-title":"Mechanism of interaction of hypoglycemic agents glimepiride and glipizide with human serum albumin","volume":"7","author":"Seedher","year":"2009","journal-title":"Open Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1007\/s001250050624","article-title":"Pharmacokinetics and safety of glimepiride at clinically effective doses in diabetic patients with renal impairment","volume":"39","author":"Rosenkranz","year":"1996","journal-title":"Diabetologia"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1055\/s-2007-979831","article-title":"Clinical evaluation of glimepiride versus glyburide in NIDDM in a double-blind comparative study. Glimepiride\/Glyburide Research Group","volume":"28","author":"Dills","year":"1996","journal-title":"Horm. Metab. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1055\/s-2007-979830","article-title":"Long-term treatment of type 2 diabetic patients with the new oral antidiabetic agent glimepiride (Amaryl): A double-blind comparison with glibenclamide","volume":"28","author":"Draeger","year":"1996","journal-title":"Horm. Metab. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.metabol.2015.02.006","article-title":"Counterregulatory responses to hypoglycemia differ between glimepiride and glyburide in non diabetic individuals","volume":"64","author":"Joy","year":"2015","journal-title":"Metabolism"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1161\/01.CIR.103.25.3111","article-title":"Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide","volume":"103","author":"Mocanu","year":"2001","journal-title":"Circulation"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/4\/1429\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:29:18Z","timestamp":1760027358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/4\/1429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,8]]},"references-count":110,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26041429"],"URL":"https:\/\/doi.org\/10.3390\/ijms26041429","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,8]]}}}