{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:08:26Z","timestamp":1792030106363,"version":"4.4.0"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,14]],"date-time":"2023-01-14T00:00:00Z","timestamp":1673654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o para Amparo da Pesquisa no Rio Grande do Sul (FAPERGS)","doi-asserted-by":"publisher","award":["21\/2551-0002062-8"],"award-info":[{"award-number":["21\/2551-0002062-8"]}],"id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Irritant contact dermatitis is usually treated with corticosteroids, which cause expressive adverse effects. Sesamol is a phenolic compound with anti-inflammatory and antioxidant properties. This study was designed to evaluate a hydrogel containing sesamol-loaded ethylcellulose nanocapsules for the treatment of irritant contact dermatitis. The nanocapsules presented a size in the nanometric range, a negative zeta potential, a sesamol content close to the theoretical value (1 mg\/mL), and a 65% encapsulation efficiency. Nanoencapsulation protected sesamol against UVC-induced degradation and increased the scavenging activity assessed by ABTS and DPPH radicals. The hydrogels were prepared by thickening the nanocapsule suspensions with guar gum (2.5%). The hydrogels maintained the nanometric size of the nanocapsules and a sesamol content of approximately 1 mg\/g. The HET-CAM assay classified the hydrogels as nonirritating. The in vitro release of the hydrogel containing sesamol in the nanoencapsulated form demonstrated an initial burst effect followed by a prolonged sesamol release and a lower skin permeation in comparison with the hydrogel containing free sesamol. In addition, it exhibited the best anti-inflammatory effect in the irritant contact dermatitis model induced by croton oil, reducing ear edema and inflammatory cells infiltration, similar to dexamethasone (positive control). Therefore, the hydrogel containing sesamol in the nanoencapsulated form seemed to have a therapeutic potential in treating irritant contact dermatitis.<\/jats:p>","DOI":"10.3390\/pharmaceutics15010285","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T03:40:34Z","timestamp":1673840434000},"page":"285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Development of Guar Gum Hydrogel Containing Sesamol-Loaded Nanocapsules Designed for Irritant Contact Dermatitis Treatment Induced by Croton Oil Application"],"prefix":"10.3390","volume":"15","author":[{"given":"Vinicius Costa","family":"Prado","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Tecnologia Farmac\u00eautica, Departamento de Farm\u00e1cia Industrial, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kauani","family":"Moenke","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Tecnologia Farmac\u00eautica, Departamento de Farm\u00e1cia Industrial, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara Felin","family":"Osmari","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Tecnologia Farmac\u00eautica, Departamento de Farm\u00e1cia Industrial, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nath\u00e1li Schopf","family":"Pegoraro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurotoxicidade e Psicofarmacologia, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Centro de Ci\u00eancias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Marchesan","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurotoxicidade e Psicofarmacologia, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Toxicol\u00f3gica, Centro de Ci\u00eancias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6230-4577","authenticated-orcid":false,"given":"Let\u00edcia","family":"Cruz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Tecnologia Farmac\u00eautica, Departamento de Farm\u00e1cia Industrial, Centro de Ci\u00eancias da Sa\u00fade, Universidade Federal de Santa Maria, Santa Maria CEP 97105-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1111\/exd.13704","article-title":"The Role of Skin Barrier in Occupational Contact Dermatitis","volume":"27","author":"Jakasa","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_2","first-page":"1","article-title":"Contact Dermatitis","volume":"7","author":"Scheinman","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5334","DOI":"10.1016\/j.bmcl.2016.09.034","article-title":"Anti-Inflammatory Activity Effect of 2-Substituted-1,4,5,6-Tetrahydrocyclopenta[b]Pyrrole on TPA-Induced Skin Inflammation in Mice","volume":"26","author":"Xu","year":"2016","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12016-018-8705-0","article-title":"Contact Dermatitis to Medications and Skin Products","volume":"56","author":"Nguyen","year":"2019","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejpb.2016.12.005","article-title":"Influence of the Skin Barrier on the Penetration of Topically-Applied Dexamethasone Probed by Soft X-Ray Spectromicroscopy","volume":"118","author":"Yamamoto","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_6","first-page":"1","article-title":"Role of Phenolic Compounds in Human Disease: Current","volume":"27","author":"Rahman","year":"2022","journal-title":"Molecules"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"988","DOI":"10.2174\/1389557520666200313120419","article-title":"An Appraisal of Current Pharmacological Perspectives of Sesamol: A Review","volume":"20","author":"Bosebabu","year":"2020","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ejphar.2019.05.008","article-title":"Sesamol, a Major Lignan in Sesame Seeds (Sesamum Indicum): Anti-Cancer Properties and Mechanisms of Action","volume":"855","author":"Majdalawieh","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.ijbiomac.2020.01.277","article-title":"Sesamol Incorporated Cellulose Acetate-Zein Composite Nanofiber Membrane: An Efficient Strategy to Accelerate Diabetic Wound Healing","volume":"149","author":"Liu","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3109\/1061186X.2014.965717","article-title":"Sesamol-Loaded Solid Lipid Nanoparticles for Treatment of Skin Cancer","volume":"23","author":"Geetha","year":"2015","journal-title":"J. Drug Target."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1517\/17425247.2013.769956","article-title":"Poly(\u03f5-Caprolactone) Microcapsules and Nanocapsules in Drug Delivery","volume":"10","author":"Coradini","year":"2013","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"122166","DOI":"10.1016\/j.ijpharm.2022.122166","article-title":"The Use of Natural Gums to Produce Nano-Based Hydrogels and Films for Topical Application","volume":"626","author":"Cruz","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.colsurfb.2019.05.029","article-title":"Film-Nanoparticle Composite for Enhanced Oral Delivery of Alpha-Casozepine","volume":"181","author":"Castro","year":"2019","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.ijbiomac.2021.03.087","article-title":"Recent Advances in Guar Gum Based Drug Delivery Systems and Their Administrative Routes","volume":"181","author":"Verma","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.carbpol.2018.10.098","article-title":"Mucoadhesive Guargum Hydrogel Inter-Connected Chitosan-g-Polycaprolactone Micelles for Rifampicin Delivery","volume":"206","author":"Yuan","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1208\/s12249-018-1240-8","article-title":"Incorporation of 3,3\u2032-Diindolylmethane into Nanocapsules Improves Its Photostability, Radical Scavenging Capacity, and Cytotoxicity Against Glioma Cells","volume":"20","author":"Mattiazzi","year":"2019","journal-title":"AAPS PharmSciTech"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.foodchem.2008.08.008","article-title":"DPPH Antioxidant Assay Revisited","volume":"113","author":"Sharma","year":"2009","journal-title":"Food Chem."},{"key":"ref_18","first-page":"1387","article-title":"Evaluation of the Spreadability of Pharmaceutical or Cosmetic Semisolid Formulations Using Scanned Images","volume":"31","author":"Rigo","year":"2012","journal-title":"Lat. Am. J. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/1523-1747.ep12533356","article-title":"Percutaneous Absorption. On the Relevance of In Vitro Data","volume":"64","author":"Franz","year":"1975","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ijpharm.2007.03.031","article-title":"Human Skin Penetration and Distribution of Nimesulide from Hydrophilic Gels Containing Nanocarriers","volume":"341","author":"Alves","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1007\/s10637-019-00823-2","article-title":"Xanthan Gum-Based Hydrogel Containing Nanocapsules for Cutaneous Diphenyl Diselenide Delivery in Melanoma Therapy","volume":"38","author":"Ferreira","year":"2020","journal-title":"Invest. New Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jphotobiol.2017.03.015","article-title":"Hydrogel Containing Silibinin-Loaded Pomegranate Oil Based Nanocapsules Exhibits Anti-Inflammatory Effects on Skin Damage UVB Radiation-Induced in Mice","volume":"170","author":"Marchiori","year":"2017","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.yrtph.2014.12.018","article-title":"Recommended Test Method Protocol: Hen\u2019s Egg Test\u2014Chorioallantoic Membrane (HET-CAM) Test Method","volume":"13","author":"Vinardell","year":"2015","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jep.2015.12.036","article-title":"Topical Anti-Inflammatory Activity of Solanum Corymbiflorum Leaves","volume":"179","author":"Piana","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"113486","DOI":"10.1016\/j.jep.2020.113486","article-title":"Oleic Acid Exhibits an Expressive Anti-Inflammatory Effect in Croton Oil-Induced Irritant Contact Dermatitis without the Occurrence of Toxicological Effects in Mice","volume":"267","author":"Pegoraro","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105500","DOI":"10.1016\/j.ejps.2020.105500","article-title":"Nanoencapsulation Potentiates the Cutaneous Anti-Inflammatory Effect of P,P\u2032-Methoxyl-Diphenyl Diselenide: Design, Permeation, and In Vivo Studies of a Nanotechnological-Based Carrageenan Gum Hydrogel","volume":"153","author":"Sari","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jep.2018.10.011","article-title":"Nasturtium Officinale R. Br. Effectively Reduces the Skin Inflammation Induced by Croton Oil via Glucocorticoid Receptor-Dependent and NF-\u039aB Pathways without Causing Toxicological Effects in Mice","volume":"229","author":"Camponogara","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104969","DOI":"10.1016\/j.ejps.2019.104969","article-title":"Hydrogel Containing Silibinin Nanocapsules Presents Effective Anti-Inflammatory Action in a Model of Irritant Contact Dermatitis in Mice","volume":"137","author":"Rigon","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4202","DOI":"10.1007\/s12035-020-01996-1","article-title":"Relevance of Mitochondrial Dysfunction in the Reserpine-Induced Experimental Fibromyalgia Model","volume":"57","author":"Brum","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for Lipid Peroxides in Animal Tissues Thiobarbituric Acid Reaction","volume":"358","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0003-9861(59)90090-6","article-title":"Tissue sulfhydryl groups","volume":"82","author":"Ellman","year":"1959","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/clt2.12045","article-title":"Topical Inflammasome Inhibition with Disulfiram Prevents Irritant Contact Dermatitis","volume":"11","author":"Bonnekoh","year":"2021","journal-title":"Clin. Transl. Allergy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00210-018-1594-1","article-title":"Cariniana Domestica Fruit Peels Present Topical Anti-Inflammatory Efficacy in a Mouse Model of Skin Inflammation","volume":"392","author":"Milani","year":"2019","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"122375","DOI":"10.1016\/j.ijpharm.2022.122375","article-title":"Development and Assessment of Phospholipid-Based Luteolin-Loaded Lipid Nanocapsules for Skin Delivery","volume":"629","author":"Elmowafy","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3236","DOI":"10.1208\/s12249-017-0810-5","article-title":"Nanoencapsulation Improves Scavenging Capacity and Decreases Cytotoxicity of Silibinin and Pomegranate Oil Association","volume":"18","author":"Marchiori","year":"2017","journal-title":"AAPS PharmSciTech"},{"key":"ref_36","first-page":"100023","article-title":"Premium Ethylcellulose Polymer Based Architectures at Work in Drug Delivery","volume":"1","author":"Adeleke","year":"2019","journal-title":"Int. J. Pharm. X"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1039\/C4RA10926K","article-title":"Biopharmaceutical Profiling of Sesamol: Physiochemical Characterization, Gastrointestinal Permeability and Pharmacokinetic Evaluation","volume":"5","author":"Geetha","year":"2015","journal-title":"RSC Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105259","DOI":"10.1016\/j.tiv.2021.105259","article-title":"Ferulic Acid-Loaded Nanocapsules: Evaluation of Mucosal Interaction, Safety and Antioxidant Activity in Human Mononucleated Cells","volume":"78","author":"Rampelotto","year":"2022","journal-title":"Toxicol. Vitr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ejps.2017.09.050","article-title":"Nanocapsules Improve Indole-3-Carbinol Photostability and Prolong Its Antinociceptive Action in Acute Pain Animal Models","volume":"111","author":"Gehrcke","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"111555","DOI":"10.1016\/j.colsurfb.2020.111555","article-title":"Development of a Nanotechnological-Based Hydrogel Containing a Novel Benzofuroazepine Compound in Association with Vitamin E: An In Vitro Biological Safety and Photoprotective Hydrogel","volume":"199","author":"Prado","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.foodres.2018.05.038","article-title":"The Simultaneous Loading of Catechin and Quercetin on Chitosan-Based Nanoparticles as Effective Antioxidant and Antibacterial Agent","volume":"111","author":"Li","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/ics.12227","article-title":"Bioadhesive Hydrogels for Cosmetic Applications","volume":"37","author":"Parente","year":"2015","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3109\/03639045.2015.1132227","article-title":"Formulation and Rheological Evaluation of Ethosome-Loaded Carbopol Hydrogel for Transdermal Application","volume":"42","author":"Jain","year":"2016","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"105150","DOI":"10.1016\/j.tiv.2021.105150","article-title":"Comparative Evaluation of HET-CAM and ICE Methods for Objective Assessment of Ocular Irritation Caused by Selected Pesticide Products","volume":"74","author":"Budai","year":"2021","journal-title":"Toxicol. Vitr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"121144","DOI":"10.1016\/j.ijpharm.2021.121144","article-title":"Pullulan Film Incorporated with Nanocapsules Improves Pomegranate Seed Oil Anti-Inflammatory and Antioxidant Effects in the Treatment of Atopic Dermatitis in Mice","volume":"609","author":"Luchese","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/exd.14308","article-title":"Effects of Constant Light Exposure on Allergic and Irritant Contact Dermatitis in Mice Reared under Constant Light Conditions","volume":"30","author":"Mizutani","year":"2021","journal-title":"Exp. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive Oxygen Species in Inflammation and Tissue Injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8852759","DOI":"10.1155\/2021\/8852759","article-title":"The Role of Oxidative Stress and Antioxidants in Diabetic Wound Healing","volume":"2021","author":"Deng","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"166287","DOI":"10.1016\/j.bbadis.2021.166287","article-title":"NMN Recruits GSH to Enhance GPX4-Mediated Ferroptosis Defense in UV Irradiation Induced Skin Injury","volume":"1868","author":"Feng","year":"2022","journal-title":"Biochim. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_50","first-page":"e61122","article-title":"Evaluation of Oxidative Stress in Biological Samples Using the Thiobarbituric Acid Reactive Substances Assay","volume":"2020","author":"Borges","year":"2020","journal-title":"J. Vis. Exp."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ejpb.2017.03.018","article-title":"P,P\u2032-Methoxyl-Diphenyl Diselenide-Loaded Polymeric Nanocapsules Are Chemically Stable and Do Not Induce Toxicity in Mice","volume":"117","author":"Ferreira","year":"2017","journal-title":"Eur. J. Pharm. Bipharm."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/1\/285\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:06:10Z","timestamp":1760119570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/1\/285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,14]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["pharmaceutics15010285"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15010285","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,14]]}}}