{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T12:07:24Z","timestamp":1775736444484,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>A new cyclodextrin polypseudorotaxanes nail lacquer (Regenail\u00ae) containing biotin, methyl sulphonyl methane (MSM), and dimethylsilanediol salicylate was developed and evaluated in vitro and in vivo. The product was developed to improve nail status and diminish signs of pathological nail alterations. A reference product (Betalfatrus\u00ae) was used for comparative purposes. An in vitro permeation experiment in hooves showed high MSM and biotin absorption. The content of sulfur and silicon in hooves was also found to be higher compared with the reference product. MSM was tested in human keratinocytes, exhibiting a good cytotoxicity profile and anti-inflammatory activity by the reduction in IL-8 and TNF-\u03b1 under LPS stimuli. A clinical study was performed to check product safety and efficacy against nail brittleness and alterations such as Beau\u2019s lines and onychorrhexis. A reduction in both alterations and in surface roughness without alteration of nail structure was observed, with a good level of patient acceptance and satisfaction.<\/jats:p>","DOI":"10.3390\/pharmaceutics12080730","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T10:45:17Z","timestamp":1596537917000},"page":"730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Transungual Delivery, Anti-Inflammatory Activity, and In Vivo Assessment of a Cyclodextrin Polypseudorotaxanes Nail Lacquer"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8224-2932","authenticated-orcid":false,"given":"Francisco","family":"Fern\u00e1ndez-Campos","sequence":"first","affiliation":[{"name":"R &amp; D Department. Reig Jofre Laboratories, Avda dels Flors, s\/n, 08970 Sant Joan Despi, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesc","family":"Navarro","sequence":"additional","affiliation":[{"name":"R &amp; D Department. Reig Jofre Laboratories, Avda dels Flors, s\/n, 08970 Sant Joan Despi, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Corrales","sequence":"additional","affiliation":[{"name":"R &amp; D Department. Reig Jofre Laboratories, Avda dels Flors, s\/n, 08970 Sant Joan Despi, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Picas","sequence":"additional","affiliation":[{"name":"R &amp; D Department. Reig Jofre Laboratories, Avda dels Flors, s\/n, 08970 Sant Joan Despi, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eloy","family":"Pena","sequence":"additional","affiliation":[{"name":"R &amp; D Department. Reig Jofre Laboratories, Avda dels Flors, s\/n, 08970 Sant Joan Despi, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"R &amp; D Department. Reig Jofre Laboratories, Avda dels Flors, s\/n, 08970 Sant Joan Despi, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-2253","authenticated-orcid":false,"given":"Francisco J.","family":"Otero-Espinar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain"},{"name":"Paraquasil Group, Health Research Institute of Santiago de Compostela (FIDIS), 15782 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/jid.1968.103","article-title":"The formation of the primate nail plate. An autoradiographic study in squirrel monkey","volume":"51","author":"Zaias","year":"1968","journal-title":"J. Investig. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Baran, R., Dawber, R.P.R., de Berker, D.A.R., Haneke, E., and Tosti, A. (2001). Science of the Nail Apparaturs. Baran and Dawber\u2019s Diseases of the Nails and Their Management, Blackwell Science.","DOI":"10.1002\/9780470694947"},{"key":"ref_3","first-page":"1025","article-title":"Histological structure of human nail as studied by synchrotron X-ray microdiffraction","volume":"46","author":"Garson","year":"2000","journal-title":"Cell. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5173(01)00989-9","article-title":"Drug delivery to the nail following topical application","volume":"236","author":"Murdan","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_5","unstructured":"Sigla, A., Neema, S., and Kumar, P. (2019). The science of nail polish, nail polish remover and nail moisturizers. Nail Disorders, a Comprehensive Approach, Taylor & Francis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/0190-9622(90)70345-I","article-title":"Treatment of brittle fingernails and onychoschizia with Biotin: Scanning electron microscopy","volume":"23","author":"Colombo","year":"1990","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1093\/rheumatology\/keh198","article-title":"Extended report: Nail disease in psoriatic Arthritis\u2014Clinically important, potentially treatable and often overlooked","volume":"43","author":"Williamson","year":"2004","journal-title":"Rheumatology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zaias, N. (1980). The Nail in Health and Disease, Springer.","DOI":"10.1007\/978-94-011-7846-4"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1067\/mjd.2000.107754","article-title":"A large-scale North American study of fungal isolates from nails: The frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns","volume":"43","author":"Ghannoum","year":"2000","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1046\/j.1365-4362.1999.00015.x","article-title":"The scope of onychomycosis: Epidemiology and clinical features","volume":"38","author":"Haneke","year":"1999","journal-title":"Int. J. Dermatol."},{"key":"ref_11","unstructured":"Sigla, A., Neema, S., and Kumar, P. (2019). Non-dermatophytic onychomycosis. Nail Disorders, a Comprehensive Approach, Taylor & Francis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/myc.12592","article-title":"Understanding the formidable nail microstructure, composition, and diseases","volume":"60","author":"Baswan","year":"2017","journal-title":"Mycoses"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rigopoulos, D., and Tosti, A. (2014). The Clinical Features of Nail Psoriasis. Nail Psoriasis from A to Z, Springer.","DOI":"10.1007\/978-3-319-08810-5"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Rigopoulos, D., and Tosti, A. (2014). Differential diagnosis of nail psoriasis. Nail Psoriasis from A to Z, Springer.","DOI":"10.1007\/978-3-319-08810-5"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1007\/s11908-000-0074-0","article-title":"Current management of onychomycosis and dermatomycoses","volume":"2","year":"2000","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_16","unstructured":"Sigla, A., Neema, S., and Kumar, P. (2019). Dermatophytic onychomycosis. Nail Disorders, a Comprehensive Approach, Taylor & Francis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1007\/s11095-007-9368-3","article-title":"Nail swelling as a pre-formulation screen for the selection and optimisation of ungual penetration enhancers","volume":"24","author":"Khengar","year":"2007","journal-title":"Pharm Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3390\/pharmaceutics10040273","article-title":"Effect of Penetration Enhancers on Drug Nail Permeability from Cyclodextrin\/Poloxamer-Soluble Polypseudorotaxane-Based Nail Lacquers","volume":"10","year":"2018","journal-title":"Pharmaceutics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"739","DOI":"10.3109\/10717544.2014.938839","article-title":"Exploring versatile applications of cyclodextrins: An overview","volume":"23","author":"Sharma","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_20","first-page":"185","article-title":"Applications of cyclodextrins in cosmetic products: A review","volume":"53","author":"Buschmann","year":"2002","journal-title":"J. Cosmet. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"950358","DOI":"10.1155\/2014\/950358","article-title":"Hydroxypropyl-\u03b2-cyclodextrin: A Novel Transungual Permeation Enhancer for Development of Topical Drug Delivery System for Onychomycosis","volume":"2014","author":"Chouhan","year":"2014","journal-title":"J. Drug Deliv."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cutr\u00edn-G\u00f3mez, E., Anguiano-Igea, S., Delgado-Charro, M.B., G\u00f3mez-Amoza, J.L., and Otero-Espinar, F.J. (2018). Otero-Espinar Effect on Nail Structure and Transungual Permeability of the Ethanol and Poloxamer Ratio from Cyclodextrin-Soluble Polypseudorotaxanes Based Nail Lacquer. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030156"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ejps.2018.02.028","article-title":"Evaluation of the promoting effect of soluble cyclodextrins in drug nail penetration","volume":"117","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1439-0507.2004.01090.x","article-title":"New insights into the effect of amorolfine nail lacquer","volume":"48","author":"Flagothier","year":"2005","journal-title":"Mycoses"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.ejpb.2012.11.004","article-title":"Thermogelling hydrogels of cyclodextrin\/poloxamer polypseudorotaxanes as aqueous-based nail lacquers: Application to the delivery of triamcinolone acetonide and ciclopirox olamine","volume":"83","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0024-3205(86)90540-0","article-title":"Incorporation of methylsulfonylmethane sulfur into guinea pig serum proteins","volume":"39","author":"Richmond","year":"1986","journal-title":"Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0003-9861(66)90182-2","article-title":"Dimethyl sulfone: Isolation from human urine","volume":"113","author":"Williams","year":"1966","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Butawan, M., Benjamin, R.L., and Bloomer, R.J. (2017). Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement. Nutrients, 9.","DOI":"10.3390\/nu9030290"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S8756-3282(02)00950-X","article-title":"Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro","volume":"32","author":"Reffitt","year":"2003","journal-title":"Bone"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1590\/abd1806-4841.20163986","article-title":"Use of silicon for skin and hair care: An approach of chemical forms available and efficacy","volume":"91","author":"Addor","year":"2016","journal-title":"An. Bras. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s00403-005-0584-6","article-title":"Effect of oral intake of choline-stabilized orthosilicic acid on skin, nails and hair in women with photodamaged skin","volume":"297","author":"Barel","year":"2005","journal-title":"Arch. Dermatol. Res."},{"key":"ref_32","first-page":"41","article-title":"Treatment of brittle fingernails with Biotin","volume":"64","author":"Floersheim","year":"1989","journal-title":"Zeitschrift fur Hautkrankh."},{"key":"ref_33","first-page":"303","article-title":"Brittle nails: Response to daily Biotin supplementation","volume":"51","author":"Hochman","year":"1993","journal-title":"Cutis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1080\/09546634.2017.1395799","article-title":"Biotin for the treatment of nail disease: What is the evidence?","volume":"29","author":"Lipner","year":"2018","journal-title":"J. Dermatol. Treat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1208\/s12249-014-0169-9","article-title":"Lateral drug diffusion in human nails","volume":"15","author":"Palliyil","year":"2014","journal-title":"AAPS PharmSciTech."},{"key":"ref_36","unstructured":"International Organization for Standardization I (2019, October 09). Biological Evaluation of Medical Devices\u2014Part 5: Tests for In Vitro Cytotoxicity, Available online: http:\/\/www.iso.org\/iso\/home\/store\/catalogue_tc\/catalogue_detail.htm?csnumber=36406."},{"key":"ref_37","first-page":"179","article-title":"Tetrazolium (MTT) assay for cellular viability and activity","volume":"79","author":"Morgan","year":"1998","journal-title":"Methods Mol. Biol."},{"key":"ref_38","first-page":"532","article-title":"A reagent for the Single-Step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples","volume":"15","author":"Chomczynski","year":"1993","journal-title":"Biotechniques"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_40","unstructured":"ICH (2020, June 30). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-q-1-e-evaluation-stability-data-step-5_en.pdf."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1021\/cr970019t","article-title":"NMR studies of cyclodextrins and cyclodextrin complexes","volume":"98","author":"Schneider","year":"1998","journal-title":"Chem. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"715","DOI":"10.2174\/138955710791572479","article-title":"Cyclodextrins: More than Pharmaceutical Excipients","volume":"10","author":"Mendez","year":"2010","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_43","first-page":"865","article-title":"Study of silicium in animal biology and during atheroma","volume":"74","author":"Loeper","year":"1966","journal-title":"La Presse Medicale"},{"key":"ref_44","first-page":"27","article-title":"Application of silicium for cosmetics. Interest of silanols in cosmetics: Silanols and cutaneous aging","volume":"28","author":"Paillet","year":"2000","journal-title":"Fragr. J."},{"key":"ref_45","first-page":"32","article-title":"Application of silicium for cosmetics. Physiological activities of silicium","volume":"28","author":"Matsumoto","year":"2000","journal-title":"Fragr. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1177\/030006059302100406","article-title":"Colloidal silicic acid for oral and topical treatment of aged skin, fragile hair and brittle nails in females","volume":"21","author":"Lassus","year":"1993","journal-title":"J. Int. Med Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) (2010). Scientific Opinion on the substantiation of health claims related to methylsulphonyl methane (MSM) and contribution to normal collagen formation (ID 353, 388, 389, 394, 1695, 1741, 1874), maintenance of normal hair (ID 353, 1741, 1874), maintenance of normal nails (ID 1695, 1741, 1874), maintenance of normal acid-base balance (ID 387), \u201cstrengthens the immune system function\u201d (ID 390), maintenance of normal bowel function (ID 391), contribution to the normal cysteine synthesis (ID 392) and \u201cvitamin production needed for correct function of metabolism\u201d (ID 393) pursuant to Article 13(1) of Regulation (EC) No 1924\/2006. EFSA J., 8, 1746.","DOI":"10.2903\/j.efsa.2010.1746"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.cyto.2014.11.001","article-title":"Methylsulfonylmethane inhibits NLRP3 inflammasome activation","volume":"71","author":"Ahn","year":"2015","journal-title":"Cytokine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1248\/bpb.32.651","article-title":"The anti-inflammatory effects of methylsulfonylmethane on lipopolysaccharide-induced inflammatory responses in murine macrophages","volume":"32","author":"Kim","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jdermsci.2012.11.002","article-title":"NF-kappaB: An essential transcription factor in psoriasis","volume":"69","author":"Goldminz","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1080\/10717540902896362","article-title":"Assessment of methylsulfonylmethane as a permeability enhancer for regional EDTA chelation therapy","volume":"16","author":"Zhang","year":"2009","journal-title":"Drug Deliv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3949\/ccjm.83a.14187","article-title":"Evaluation of nail lines: Color and shape hold clues","volume":"83","author":"Scher","year":"2016","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.jaad.2015.08.003","article-title":"Beau lines, onychomadesis, and retronychia: A unifying hypothesis","volume":"73","author":"Braswell","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.pop.2015.08.005","article-title":"Nail Deformities and Injuries","volume":"42","author":"Tucker","year":"2015","journal-title":"Prim. Care Clin. Off. Pract."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s13555-019-00338-x","article-title":"Pathogenesis, Clinical Signs and Treatment Recommendations in Brittle Nails: A Review","volume":"10","author":"Chessa","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_56","first-page":"1089","article-title":"Effect of urea nail lacquer on nail quality. Clinical evaluation and biophysical measurements","volume":"57","author":"Krueger","year":"2007","journal-title":"Der Hautarzt Zeitschrift f\u00fcr Dermatol. Venerol. Verwandte Geb."},{"key":"ref_57","first-page":"31","article-title":"Equisetum arvense in a new transungual technology imporves nail structure and appearance","volume":"2","author":"Sparavigna","year":"2006","journal-title":"J. Plast. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Cutr\u00edn-G\u00f3mez, E., Conde-Penedo, A., Anguiano-Igea, S., G\u00f3mez-Amoza, J.L., and Otero-Espinar, F.J. (2020). Optimization of Drug Permeation from 8% Ciclopirox Cyclodextrin\/Poloxamer-Soluble Polypseudorotaxane-Based Nail Lacquers. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12030231"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/8\/730\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:54:10Z","timestamp":1760176450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/8\/730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,4]]},"references-count":58,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["pharmaceutics12080730"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12080730","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,4]]}}}