{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:47:43Z","timestamp":1760150863409,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T00:00:00Z","timestamp":1643500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BDE\/11062\/2015","UIDB\/04035\/2020"],"award-info":[{"award-number":["SFRH\/BDE\/11062\/2015","UIDB\/04035\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Applied Sciences"],"abstract":"<jats:p>Pelotherapy and electrotherapy are therapeutic methodologies with proven success in physical medicine and rehabilitation (PMR) and dermatology fields. The main purpose of these therapeutic modalities is to reduce pain, accelerate wound healing, alleviate muscle spasms, and improve mobility, and muscle tone. Their main challenge is in the passage of some ionic species through the skin barrier. The use of drugs, such as diclofenac, corticosteroids or steroids, has gained widespread efficacy recognition in physical therapy and the therapeutic action of these drugs is widely studied in experimental and clinical trials. Unlike pharmaceutical and cosmetic clays, peloids are not subject to any prior quality control or subject to any specific European regulation. The dermal absorption values are an integral part of the risk assessment process for peloids. This work explores the converging points between these two transdermal drug delivery systems (TDDS) and the presentation of methodologies to achieve peloid safety compliance, especially concerning the potential and degree of toxicity arising from ion exchange and trace elements. TDDS is applied to the pharmaceuticals industry and drug is the generic term for the active substances released into skin tissues. The transdermal delivery of drugs or clay components with therapeutic properties is limited due to the excellent barrier function of the stratum corneum. The transdermal drug delivery of pelotherapy is enhanced by temperature and electrically by iontophoresis. The low voltage of iontophoresis and sweat phenomena with pore dilation driven by pelotherapy allows the use of the same pathways: hair follicles and sweat pore. The therapeutic integration of iontophoresis and pelotherapy focused on patient benefits and low safety-related risk may contribute to the outstanding physiological performance of pelotherapy, specifically, in the way the essential elements and exchange cations pass through the skin barrier. The validation of an innovative iontophoretic systems applied to pelotherapy can also promote future challenges in the obtaining of the ideal therapeutic control of peloids and the clinical validation of results with physiological efficacy recognition.<\/jats:p>","DOI":"10.3390\/app12031509","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T01:46:08Z","timestamp":1643593568000},"page":"1509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The Challenge in Combining Pelotherapy and Electrotherapy (Iontophoresis) in One Single Therapeutic Modality"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5074-4137","authenticated-orcid":false,"given":"Carla Marina","family":"Bastos","sequence":"first","affiliation":[{"name":"GeoBioTec Research Centre, Department of Geosciences, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Exatronic, Lda., 3800-373 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3636-3933","authenticated-orcid":false,"given":"Fernando","family":"Rocha","sequence":"additional","affiliation":[{"name":"GeoBioTec Research Centre, Department of Geosciences, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Nuno","family":"Gomes","sequence":"additional","affiliation":[{"name":"Exatronic, Lda., 3800-373 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0922-8290","authenticated-orcid":false,"given":"Paula","family":"Marinho-Reis","sequence":"additional","affiliation":[{"name":"Institute of Earth Sciences (ICT), Pole of the University of Minho, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1272\/jnms.JNMS.2018_85-30","article-title":"Evaluation of the Role of Balneotherapy in Rehabilitation Medicine","volume":"85","author":"Matsumoto","year":"2018","journal-title":"J. Nippon Med. Sch."},{"key":"ref_2","first-page":"129","article-title":"A utiliza\u00e7\u00e3o das lamas em Portugal: Passado e presente","volume":"4","author":"Teixeira","year":"2011","journal-title":"Anales Hidrol. M\u00e9d."},{"key":"ref_3","unstructured":"World Health Organization (2013). WHO Traditional Medicine Strategy: 2014\u20132023, WHO Publications."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00296-010-1628-6","article-title":"Mechanisms of action of spa therapies in rheumatic diseases: What scientific evidence is there?","volume":"31","author":"Fioravanti","year":"2011","journal-title":"Rheumatol. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s00484-019-01731-z","article-title":"Spa therapy and rehabilitation of musculoskeletal pathologies: A proposal for best practice in Italy","volume":"64","author":"Bernetti","year":"2020","journal-title":"Inter. J. Biometeorol."},{"key":"ref_6","first-page":"38","article-title":"Peloterapia, una revisi\u00f3n","volume":"9","author":"Maraver","year":"2015","journal-title":"Med. Natur."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.clay.2013.02.008","article-title":"Peloids and pelotherapy: Historical evolution, classification and glossary","volume":"75","author":"Gomes","year":"2013","journal-title":"Appl. Clay Sci."},{"key":"ref_8","first-page":"99","article-title":"Health resort treatment\u2014A new chance for the treatment of vessel diseases?","volume":"16","author":"Pasek","year":"2010","journal-title":"Acta Angiol."},{"key":"ref_9","first-page":"22","article-title":"Physical and Rehabilitation Medicine: The Medical Specialty","volume":"18","author":"Amaro","year":"2009","journal-title":"Rev. Soc. Port. Med. F\u00eds. Reabil."},{"key":"ref_10","first-page":"176","article-title":"Skin Port: A Novel Route for Drug Delivery","volume":"12","author":"Akhlaq","year":"2014","journal-title":"Gomal. J. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2174\/15672018113106660064","article-title":"Vesicles: A recently developed novel carrier for enhanced topical drug delivery","volume":"11","author":"Akhtar","year":"2014","journal-title":"Curr. Drug Deliv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1180\/claymin.2012.047.4.04","article-title":"Certification and quality criteria of peloids used for therapeutic purposes","volume":"47","author":"Quintela","year":"2012","journal-title":"Clay Miner."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.clay.2006.08.006","article-title":"Minerals and clay minerals in medical geology","volume":"36","author":"Gomes","year":"2007","journal-title":"Appl. Clay. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.clay.2006.06.015","article-title":"Use of clays as drug delivery systems: Possibilities and limitations","volume":"36","author":"Aguzzi","year":"2007","journal-title":"Appl. Clay Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0169-1317(01)00085-0","article-title":"Clay minerals and their beneficial effects upon human health. A review","volume":"21","author":"Carretero","year":"2002","journal-title":"Appl. Clay Sci."},{"key":"ref_16","unstructured":"Francois, G., Micollier, A., and Rouvie, I. (2005). Les Boues Thermales, Atelier Sant\u00e9 Environnement: ENSP (\u00c9cole Nationale de la Sant\u00e9 Publique)."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.ejpb.2012.03.019","article-title":"Understanding heat facilitated drug transport across human epidermis","volume":"81","author":"Wood","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"135","DOI":"10.23853\/bsehm.2017.0385","article-title":"O termalismo na Regi\u00e3o Centro","volume":"30","author":"Teixeira","year":"2015","journal-title":"Bol. Soc. Esp. Hidrol. M\u00e9d."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1590\/S1806-00132012000100012","article-title":"Physical therapy action mechanisms and effects on pain management","volume":"13","author":"Gosling","year":"2013","journal-title":"Rev. Dor"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yam, M.F., Loh, Y.C., Tan, C.S., Adam, S.K., Manan, N.A., and Basir, R. (2018). General Pathways of Pain Sensation and the Major Neurotransmitters Involved in Pain Regulation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082164"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1097\/00044067-200507000-00003","article-title":"The endogenous opioid system and clinical pain management","volume":"16","author":"Holden","year":"2005","journal-title":"AACN Clin. Issues"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1097\/00000542-199911000-00012","article-title":"Effect of the Frequency of Transcutaneous Electrical Nerve Stimulation on the Postoperative Opioid Analgesic Requirement and Recovery Profile","volume":"91","author":"Hamza","year":"1999","journal-title":"Anesthesiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/bcp.12128","article-title":"and Cracowski, JL. Trials and tribulations of skin iontophoresis in therapeutics","volume":"77","author":"Roustit","year":"2014","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/S1367-5931(00)00111-3","article-title":"Transdermal iontophoresis revisited","volume":"4","author":"Panchagnula","year":"2000","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2165\/00063030-200216050-00003","article-title":"Iontophoresis-based transdermal delivery systems","volume":"16","author":"Kanikkannan","year":"2002","journal-title":"BioDrugs"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0168-3659(99)00262-X","article-title":"The effect of electroporation on iontophoretic transdermal delivery of calcium regulating hormones","volume":"66","author":"Chang","year":"2000","journal-title":"J. Control Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.addr.2013.11.014","article-title":"Effective use of transdermal drug delivery in children","volume":"73","author":"Guy","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1590\/S1413-35552009000600006","article-title":"Electrical resistance of gels and liquids used in electrotherapy for electrode-skin coupling","volume":"13","author":"Bolfe","year":"2009","journal-title":"Rev. Bras. Fisioter. S\u00e3o Carlos"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0882-5963(05)80052-1","article-title":"lontophoresis for Pain Management","volume":"10","author":"Mcfadden","year":"1995","journal-title":"J. Pediatr. Nurs."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"20780","DOI":"10.3390\/molecules191220780","article-title":"Prodrug strategies for enhancing the percutaneous absorption of drugs","volume":"19","year":"2014","journal-title":"Molecules"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.reprotox.2015.10.001","article-title":"What happens in the skin? Integrating skin permeation kinetics into studies of developmental and reproductive toxicity following topical exposure","volume":"58","author":"Dancik","year":"2015","journal-title":"Reprod. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"125","DOI":"10.2174\/156720110791011765","article-title":"Electroporation: An Avenue for transdermal Drug Delivery","volume":"7","author":"Naseem","year":"2010","journal-title":"Curr. Drug Deliv."},{"key":"ref_33","first-page":"750","article-title":"The Topical\/Transdermal Ad Hoc Advisory Panel for the USP Performance Tests of Topical and Transdermal Dosage Forms. Topical and transdermal drug products","volume":"35","author":"Ueda","year":"2009","journal-title":"Pharmacop. Forum."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1016\/S0169-409X(02)00113-8","article-title":"Drug delivery routes in skin: A novel approach","volume":"54","author":"Barry","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1180\/claymin.2014.049.1.03","article-title":"Abrasiveness index of dispersions of Portuguese clays using the Einlehner method: Influence of clay parameters","volume":"49","author":"Quintela","year":"2014","journal-title":"Clay Miner."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.clay.2017.12.017","article-title":"Characterization of Andalusian peats for skin health care formulations","volume":"160","author":"Carazo","year":"2018","journal-title":"Appl. Clay Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0168-3659(99)00132-7","article-title":"Iontophoresis: Electrorepulsion and electroosmosis","volume":"64","author":"Guy","year":"2000","journal-title":"J. Control Release"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s00484-020-01911-2","article-title":"Balneotherapy for knee osteoarthritis in S. Jorge: A randomized controlled trial","volume":"64","author":"Cantista","year":"2020","journal-title":"Int. J. Biometeorol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s00484-019-01764-4","article-title":"The effects of Tiszas\u00fcly and kolop mud pack therapy on knee osteoarthritis: A double-blind, randomised, non-inferiority controlled study","volume":"64","author":"Hodosi","year":"2020","journal-title":"Int. J. Biometeorol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1042576","DOI":"10.1155\/2018\/1042576","article-title":"Efficacy of Spa Therapy, Mud-Pack Therapy, Balneotherapy, and Mud-Bath Therapy in the Management of Knee Osteoarthritis. A Systematic Review","volume":"2018","author":"Fraioli","year":"2018","journal-title":"BioMed. Res. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1007\/s00484-016-1138-7","article-title":"Spa therapy for elderly: A retrospective study of 239 older patients with osteoarthritis","volume":"60","year":"2016","journal-title":"Int. J. Biometerol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.joca.2014.01.003","article-title":"OARSI guidelines for the non-surgical management of knee osteoarthritis","volume":"22","author":"McAlindon","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_43","first-page":"109","article-title":"Effects of mud pack therapy on patients with knee osteoarthritis. A randomized controlled clinical trial","volume":"5","author":"Espejo","year":"2012","journal-title":"Anales Hidrol. M\u00e9d."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0009-8981(97)00171-X","article-title":"Mud pack therapy in osteoarthrosis. Changes in serum levels of chondrocyte markers","volume":"268","author":"Bellometti","year":"1997","journal-title":"Clin. Chim. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.clay.2009.02.004","article-title":"The in-vitro percutaneous migration of chemical elements from a thermal mud for healing use","volume":"44","author":"Tateo","year":"2009","journal-title":"Appl. Clay Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.jbspin.2006.12.003","article-title":"Mud-bath treatment in spondylitis associated with inflammatory bowel disease\u2014A pilot randomised clinical trial","volume":"74","author":"Cozzi","year":"2007","journal-title":"Joint Bone Spine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0753-3322(96)85097-9","article-title":"Mud pack treatment increases serum antioxidant defenses in osteoarthritic patients","volume":"50","author":"Bellometti","year":"1996","journal-title":"Biomed. Pharmacother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jconrel.2012.09.017","article-title":"Approaches for breaking the barriers of drug permeation through transdermal drug delivery","volume":"164","author":"Alexander","year":"2012","journal-title":"J. Control Release"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1001\/archderm.1941.01500050030003","article-title":"Iontophoresis of copper sulfate in cases of proved mycotic infection","volume":"44","author":"Greenwood","year":"1941","journal-title":"Arch. Derm. Syphilol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1001\/jama.1939.02800130013005","article-title":"Fungous infections of the hands and feet treated by iontophoresis of copper: Preliminary Report","volume":"112","author":"Haggard","year":"1939","journal-title":"JAMA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/ptj\/38.2.96","article-title":"The Use of Magnesium Sulphate Iontophoresis in the Treatment of Subdeltoid Bursitis","volume":"38","author":"Weinstein","year":"1958","journal-title":"Phys. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2519\/jospt.1982.4.2.113","article-title":"A Case Report: Lithium Iontophoresis for Gouty Arthritis","volume":"4","author":"Kahn","year":"1982","journal-title":"J. Orthop. Sports Phys. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"871","DOI":"10.2106\/00004623-197860070-00001","article-title":"Treatment of orthopaedic infections with electrically generated silver ions. A preliminary report","volume":"60","author":"Becker","year":"1978","journal-title":"J. Bone Joint Surg. Am."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.4103\/njcp.njcp_341_17","article-title":"Iontophoresis and topical application of 8% arginine-calcium carbonate to treat dentinal hypersensitivity","volume":"21","author":"Kumar","year":"2018","journal-title":"Niger. J. Clin. Pract."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2522\/ptj.20100400","article-title":"In Vivo Calcium and Phosphate Iontophoresis for the Topical Treatment of Osteoporosis","volume":"92","author":"Gomez","year":"2012","journal-title":"Phys. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1590\/S0102-86502013000800008","article-title":"Zinc sulphate administered by transdermal iontophoresis improves breaking strength of surgical wounds in skin of alloxan-induced diabetic rats","volume":"28","author":"Cassettari","year":"2013","journal-title":"Acta Cir. Bras."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/ptj\/61.3.359","article-title":"Zinc Iontophoresis to Treat Ischemic Skin Ulcers","volume":"61","author":"Cornwall","year":"1981","journal-title":"Phys. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.jep.2014.06.031","article-title":"Folk pharmaceutical formulations in western Mediterranean: Identification and safety of clays used in pelotherapy","volume":"155","author":"Aguzzi","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_59","first-page":"2502","article-title":"Current status and future innovations in transdermal drug delivery","volume":"3","author":"Chhabaria","year":"2012","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0168-3659(98)00092-3","article-title":"Effect of the different factors on the iontophoretic delivery of calcium ions from bentonite","volume":"56","author":"Papp","year":"1998","journal-title":"J. Control Release"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3109\/1061186X.2015.1090442","article-title":"Transdermal iontophoretic drug delivery: Advances and challenges","volume":"24","author":"Ita","year":"2016","journal-title":"J. Drug Target."}],"container-title":["Applied Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3417\/12\/3\/1509\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:11:30Z","timestamp":1760134290000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3417\/12\/3\/1509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,30]]},"references-count":61,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["app12031509"],"URL":"https:\/\/doi.org\/10.3390\/app12031509","relation":{},"ISSN":["2076-3417"],"issn-type":[{"type":"electronic","value":"2076-3417"}],"subject":[],"published":{"date-parts":[[2022,1,30]]}}}