{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:25:30Z","timestamp":1779164730170,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"OTKA_NKFIH-K-134214","award":["TKP2021-EGA-13"],"award-info":[{"award-number":["TKP2021-EGA-13"]}]},{"name":"OTKA_NKFIH-K-134214","award":["RRF-2.3.1-21-2022-00015"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00015"]}]},{"name":"National Research, Development, and Innovation Fund of Hungary","award":["TKP2021-EGA-13"],"award-info":[{"award-number":["TKP2021-EGA-13"]}]},{"name":"National Research, Development, and Innovation Fund of Hungary","award":["RRF-2.3.1-21-2022-00015"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00015"]}]},{"name":"National Research, Development and Innovation Office","award":["TKP2021-EGA-13"],"award-info":[{"award-number":["TKP2021-EGA-13"]}]},{"name":"National Research, Development and Innovation Office","award":["RRF-2.3.1-21-2022-00015"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>There is an unmet need for novel therapeutic tools relieving chronic pain. Hydrogen sulfide (H2S) is highly involved in pain processes; however, the development of ideal matrices for sulfide donor compounds remains a great pharmaceutical challenge. We aimed to establish a suitable transdermal therapeutic system (TTS) using the H2S donor diallyl disulfide (DADS) as a model compound. After the preparation of DADS, its solubility was investigated in different liquid excipients (propylene glycol, polyethylene glycol, silicone oil) and its membrane diffusivity was assessed in silicone matrices of different compositions. Drug-releasing properties of DADS-containing patches with different silicone oil contents were determined with Franz and flow-through cells. We found a correlation between the liquid excipient content of the patch and the diffusion rate of DADS. DADS showed the best solubility in dimethyl silicone oil, and the diffusion constant was proportional to the amount of oil above the 3 m\/m% threshold value. The 8-day-old patch showed a significantly lower, but better-regulated, drug release over time than the 4-day-old one. In conclusion, the silicone-based polymer matrix developed in this study is suitable for stable storage and optimal release of DADS, providing a good basis for a TTS applied in chronic pain.<\/jats:p>","DOI":"10.3390\/ph15101182","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T03:34:17Z","timestamp":1664163257000},"page":"1182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Development of a Silicone-Based Polymer Matrix as a Suitable Transdermal Therapeutic System for Diallyl Disulfide"],"prefix":"10.3390","volume":"15","author":[{"given":"Szabolcs","family":"L\u00e1szl\u00f3","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, Szigeti u. 12., H-7624 P\u00e9cs, Hungary"},{"name":"Department of Inorganic and Analytical Chemistry, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, M\u0171egyetem rkp. 3., H-1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zs\u00f3fia","family":"Hajna","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, Szigeti u. 12., H-7624 P\u00e9cs, Hungary"},{"name":"Molecular Pharmacology Research Group, Szent\u00e1gothai Research Centre, University of P\u00e9cs, Ifj\u00fas\u00e1g \u00fa. 20., H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"Egyed","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Magyar Tud\u00f3sok K\u00f6r\u00fatja 2., H-1117 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9898-632X","authenticated-orcid":false,"given":"Erika","family":"Pint\u00e9r","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Medical School, University of P\u00e9cs, Szigeti u. 12., H-7624 P\u00e9cs, Hungary"},{"name":"Molecular Pharmacology Research Group, Szent\u00e1gothai Research Centre, University of P\u00e9cs, Ifj\u00fas\u00e1g \u00fa. 20., H-7624 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6d\u00f6n","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, M\u0171egyetem rkp. 3., H-1111 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ejpain.2005.06.009","article-title":"Survey of Chronic Pain in Europe: Prevalence, Impact on Daily Life, and Treatment","volume":"10","author":"Breivik","year":"2006","journal-title":"Eur. J. Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e779","DOI":"10.1097\/PR9.0000000000000779","article-title":"Prevalence of Chronic Pain in Developing Countries: Systematic Review and Meta-Analysis","volume":"4","author":"Moreira","year":"2019","journal-title":"Pain Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1055\/s-0035-1558983","article-title":"Autonomic Neuropathy","volume":"35","author":"Dineen","year":"2015","journal-title":"Semin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.18773\/austprescr.2018.022","article-title":"Neuropathic Pain: Current Definition and Review of Drug Treatment","volume":"41","author":"Murnion","year":"2018","journal-title":"Aust. Prescr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"114108","DOI":"10.1016\/j.expneurol.2022.114108","article-title":"Neurogenic Inflammation as a Novel Treatment Target for Chronic Pain Syndromes","volume":"356","author":"Seidel","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref_6","unstructured":"(2022, August 12). Physiological Roles of Hydrogen Sulfide in Mammalian Cells, Tissues and Organs|Physiological Reviews. Available online: https:\/\/journals.physiology.org\/doi\/abs\/10.1152\/physrev.00028.2021."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"173322","DOI":"10.1016\/j.ejphar.2020.173322","article-title":"Role of H2S in Pain: Growing Evidences of Mystification","volume":"883","author":"Guo","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.bcp.2017.11.014","article-title":"A Review of Hydrogen Sulfide (H2S) Donors: Chemistry and Potential Therapeutic Applications","volume":"149","author":"Powell","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Moore, P.K., and Whiteman, M. (2015). Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors. Chemistry, Biochemistry and Pharmacology of Hydrogen Sulfide, Springer International Publishing. Handbook of Experimental Pharmacology.","DOI":"10.1007\/978-3-319-18144-8_17"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11788","DOI":"10.1039\/C4CC00968A","article-title":"Hydrogen Sulfide (H2S) Releasing Agents: Chemistry and Biological Applications","volume":"50","author":"Zhao","year":"2014","journal-title":"Chem. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1002\/med.21913","article-title":"Progress and Perspective on Hydrogen Sulfide Donors and Their Biomedical Applications","volume":"42","author":"Song","year":"2022","journal-title":"Med. Res. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12248","DOI":"10.1073\/pnas.0505356102","article-title":"Pungent Products from Garlic Activate the Sensory Ion Channel TRPA1","volume":"102","author":"Bautista","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4196","DOI":"10.1021\/acs.orglett.5b01962","article-title":"Diallyl Trisulfide Is a Fast H 2 S Donor, but Diallyl Disulfide Is a Slow One: The Reaction Pathways and Intermediates of Glutathione with Polysulfides","volume":"17","author":"Liang","year":"2015","journal-title":"Org. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/ejp.1935","article-title":"Antinociceptive Effect of Garlic Garlic Preparations and Derivative compounds","volume":"26","author":"Maldonado","year":"2022","journal-title":"Eur. J. Pain"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5103626","DOI":"10.1155\/2021\/5103626","article-title":"Biological Functions of Diallyl Disulfide, a Garlic-Derived Natural Organic Sulfur Compound","volume":"2021","author":"Song","year":"2021","journal-title":"Evid. Based Complementary Altern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"216","DOI":"10.3344\/kjp.2020.33.3.216","article-title":"Exploring the Role and Mechanisms of Diallyl Trisulfide and Diallyl Disulfide in Chronic Constriction-Induced Neuropathic Pain in Rats","volume":"33","author":"Wang","year":"2020","journal-title":"Korean J Pain"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Porta, A., Rodr\u00edguez, L., Bai, X., Batall\u00e9, G., Roch, G., Pouso-V\u00e1zquez, E., Balboni, G., and Pol, O. (2021). Hydrogen Sulfide Inhibits Inflammatory Pain and Enhances the Analgesic Properties of Delta Opioid Receptors. Antioxidants, 10.","DOI":"10.3390\/antiox10121977"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.jfda.2014.04.002","article-title":"Sulfur Compounds Identification and Quantification from Allium spp. Fresh Leaves","volume":"22","author":"Neagu","year":"2014","journal-title":"J. Food Drug Anal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s11771-006-0079-4","article-title":"Synthesis, Characterization and Bioactivity Evaluation of Diallyl Disulfide","volume":"13","author":"Yuan","year":"2006","journal-title":"J Cent. South Univ. Technol."},{"key":"ref_20","first-page":"279","article-title":"Silicone Polymers in Controlled Drug Delivery Systems: A Review","volume":"18","author":"Mashak","year":"2009","journal-title":"Iran. Polym. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jconrel.2021.11.025","article-title":"Recent Advances in Polymeric Transdermal Drug Delivery Systems","volume":"341","author":"Sabbagh","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1600-0846.2008.00316.x","article-title":"Delivering Drugs by the Transdermal Route: Review and Comment","volume":"14","author":"Tanner","year":"2008","journal-title":"Skin Res. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jconrel.2008.08.012","article-title":"The Origins and Evolution of \u201cControlled\u201d Drug Delivery Systems","volume":"132","author":"Hoffman","year":"2008","journal-title":"J. Control. Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1111\/bph.13059","article-title":"Transdermal Patches: History, Development and Pharmacology","volume":"172","author":"Pastore","year":"2015","journal-title":"Br. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3109\/03639049809085616","article-title":"Development of a New Silicon-Based Transdermal System. I. Study of Silicone Elastomers and Effect of Liquid Ingredients","volume":"24","author":"Wagner","year":"1998","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1023\/A:1021247513273","article-title":"Development of a New Silicone Base Transdermal Therapeutic System","volume":"1","author":"Wagner","year":"2002","journal-title":"Silicon Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1002\/app.1952","article-title":"Development of a New Silicone-base Transdermal Therapeutic System II Study of Study of trifunctional ingredients","volume":"82","author":"Wagner","year":"2001","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_28","first-page":"169","article-title":"A New Transdermal System I","volume":"35","author":"Wagner","year":"1991","journal-title":"Period. Polytech. Chem. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.3109\/03639048509059868","article-title":"Simple Evaluation Method of Intrinsic Diffusivity for Membrane-Moderated Controlled Release","volume":"11","author":"Tojo","year":"1985","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1208\/s12249-010-9522-9","article-title":"Validation of a Static Franz Diffusion Cell System for in Vitro Permeation Studies","volume":"11","author":"Ng","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s12668-020-00767-5","article-title":"Poloxamer-Based In Situ Nasal Gel of Naratriptan Hydrochloride Deformable Vesicles for Brain Targeting","volume":"10","author":"Shelke","year":"2020","journal-title":"BioNanoScience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1080\/09546634.2020.1789043","article-title":"Mometasone Furoate-Loaded Aspasomal Gel for Topical Treatment of Psoriasis: Formulation, Optimization, in Vitro and in Vivo Performance","volume":"33","author":"Shinde","year":"2022","journal-title":"J. Dermatol. Treat."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Corvino, A., Frecentese, F., Magli, E., Perissutti, E., Santagada, V., Scognamiglio, A., Caliendo, G., Fiorino, F., and Severino, B. (2021). Trends in H2S-Donors Chemistry and Their Effects in Cardiovascular Diseases. Antioxidants, 10.","DOI":"10.3390\/antiox10030429"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1152\/physrev.00005.2019","article-title":"Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease","volume":"100","author":"Talavera","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1080\/14728222.2020.1815191","article-title":"TRPA1 as a Therapeutic Target for Nociceptive Pain","volume":"24","author":"Nassini","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"136286","DOI":"10.1016\/j.neulet.2021.136286","article-title":"Mini-Review: The Nociceptive Sensory Functions of the Polymodal Receptor Transient Receptor Potential Ankyrin Type 1 (TRPA1)","volume":"764","author":"Manolache","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1111\/bph.14514","article-title":"Effects of Sulfide and Polysulfides Transmitted by Direct or Signal Transduction-Mediated Activation of TRPA1 Channels: TRPA1-Mediated Effects of Sulfide and Polysulfides","volume":"176","author":"Pozsgai","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1177\/1535370220918193","article-title":"Hydrogen Sulfide Attenuates Diabetic Neuropathic Pain through NO\/CGMP\/PKG Pathway and \u03bc-Opioid Receptor","volume":"245","author":"Li","year":"2020","journal-title":"Exp. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Dombi, \u00c1., S\u00e1nta, C., B\u00e1tai, I.Z., Kormos, V., Kecsk\u00e9s, A., T\u00e9kus, V., Poh\u00f3czky, K., B\u00f6lcskei, K., Pint\u00e9r, E., and Pozsgai, G. (2021). Dimethyl Trisulfide Diminishes Traumatic Neuropathic Pain Acting on TRPA1 Receptors in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073363"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1007\/s40265-018-0982-7","article-title":"Capsaicin 8% Dermal Patch: A Review in Peripheral Neuropathic Pain","volume":"78","author":"Blair","year":"2018","journal-title":"Drugs"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1161\/CIRCULATIONAHA.107.753467","article-title":"Characterization of a Novel, Water-Soluble Hydrogen Sulfide\u2013Releasing Molecule (GYY4137): New Insights Into the Biology of Hydrogen Sulfide","volume":"117","author":"Li","year":"2008","journal-title":"Circulation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.neuint.2013.04.001","article-title":"Differential Mechanisms Underlying Neuroprotection of Hydrogen Sulfide Donors against Oxidative Stress","volume":"62","author":"Jia","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.niox.2014.04.008","article-title":"AP39, a Novel Mitochondria-Targeted Hydrogen Sulfide Donor, Stimulates Cellular Bioenergetics, Exerts Cytoprotective Effects and Protects against the Loss of Mitochondrial DNA Integrity in Oxidatively Stressed Endothelial Cells in Vitro","volume":"41","author":"Szczesny","year":"2014","journal-title":"Nitric Oxide"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.exer.2015.04.001","article-title":"Inhibitory Action of Novel Hydrogen Sulfide Donors on Bovine Isolated Posterior Ciliary Arteries","volume":"134","author":"Mitchell","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.phrs.2016.08.019","article-title":"The Novel Mitochondria-Targeted Hydrogen Sulfide (H2S) Donors AP123 and AP39 Protect against Hyperglycemic Injury in Microvascular Endothelial Cells in Vitro","volume":"113","author":"Torregrossa","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.phrs.2016.09.032","article-title":"A Novel Slow-Releasing Hydrogen Sulfide Donor, FW1256, Exerts Anti-Inflammatory Effects in Mouse Macrophages and in Vivo","volume":"113","author":"Huang","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6193","DOI":"10.1039\/C9CC02829C","article-title":"Controllable Thioester-Based Hydrogen Sulfide Slow-Releasing Donors as Cardioprotective Agents","volume":"55","author":"Yao","year":"2019","journal-title":"Chem. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1021\/bc500150s","article-title":"Design and Synthesis of Polymeric Hydrogen Sulfide Donors","volume":"25","author":"Hasegawa","year":"2014","journal-title":"Bioconjug. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s11095-021-03164-z","article-title":"Transdermal Delivery of a Hydrogen Sulphide Donor, ADT-OH Using Aqueous Gel Formulations for the Treatment of Impaired Vascular Function: An Ex Vivo Study","volume":"39","author":"Marwah","year":"2022","journal-title":"Pharm. Res."},{"key":"ref_50","first-page":"198","article-title":"Intelligent Polymeric Hydrogen Sulfide Delivery Systems for Therapeutic Applications","volume":"19","author":"Rong","year":"2023","journal-title":"Bioact. Mater."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/10\/1182\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:38:04Z","timestamp":1760143084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/10\/1182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ph15101182"],"URL":"https:\/\/doi.org\/10.3390\/ph15101182","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]}}}