{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:01:10Z","timestamp":1771927270664,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2017,11,28]],"date-time":"2017-11-28T00:00:00Z","timestamp":1511827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES, Brazil)"},{"name":"Secretar\u00eda de Educaci\u00f3n Superior, Ciencia, Tecnolog\u00eda e Innovaci\u00f3n (Sensescyt \u2013 Ecuador) and Universidad T\u00e9cnica Particular de Loja - Ecuador"},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["MAT2014-59134R"],"award-info":[{"award-number":["MAT2014-59134R"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rosacea is the most common inflammatory skin disease. It is characterized by erythema, inflammatory papules and pustules, visible blood vessels, and telangiectasia. The current treatment has limitations and unsatisfactory results. Pioglitazone (PGZ) is an agonist of peroxisome proliferator-activated receptors (PPARs), a nuclear receptor that regulates important cellular functions, including inflammatory responses. The purpose of this study was to evaluate the permeation of PGZ with a selection of penetration enhancers and to analyze its effectiveness for treating rosacea. The high-performance liquid chromatography (HPLC) method was validated for the quantitative determination of PGZ. Ex vivo permeation experiments were realized in Franz diffusion cells using human skin, in which PGZ with different penetration enhancers were assayed. The results showed that the limonene was the most effective penetration enhancer that promotes the permeation of PGZ through the skin. The cytotoxicity studies and the Draize test detected cell viability and the absence of skin irritation, respectively. The determination of the skin color using a skin colorimetric probe and the results of histopathological studies confirmed the ability of PGZ-limonene to reduce erythema and vasodilation. This study suggests new pharmacological indications of PGZ and its possible application in the treatment of skin diseases, namely rosacea.<\/jats:p>","DOI":"10.3390\/ijms18122548","type":"journal-article","created":{"date-parts":[[2017,11,28]],"date-time":"2017-11-28T11:23:50Z","timestamp":1511868230000},"page":"2548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Human Skin Permeation Studies with PPAR\u03b3 Agonist to Improve Its Permeability and Efficacy in Inflammatory Processes"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9906-049X","authenticated-orcid":false,"given":"Marcelle","family":"Silva-Abreu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1486-5622","authenticated-orcid":false,"given":"Lupe","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Departamento de Qu\u00edmica y Ciencias Exactas, Universidad T\u00e9cnica Particular de Loja, Loja 1101608, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7870-8250","authenticated-orcid":false,"given":"Mar\u00eda","family":"Rodr\u00edguez-Lagunas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institut de Recerca en Nutrici\u00f3 i Seguretat Aliment\u00e0ria (INSA), Universitat de Barcelona (UB), 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3335-5567","authenticated-orcid":false,"given":"Mar\u00eda-Jos\u00e9","family":"F\u00e1brega","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1269-3847","authenticated-orcid":false,"given":"Marta","family":"Espina","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-4821","authenticated-orcid":false,"given":"Ana","family":"Calpena","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.jaad.2016.11.065","article-title":"Risk of inflammatory bowel disease in patients with rosacea: Results from a nationwide cohort study in Taiwan","volume":"76","author":"Wu","year":"2017","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.jaad.2015.11.004","article-title":"Clustering of autoimmune diseases in patients with rosacea","volume":"74","author":"Egeberg","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.amjoto.2016.01.009","article-title":"Otophyma: A rare variant of phymatous rosacea","volume":"37","year":"2016","journal-title":"Am. J. Otolaryngol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jaad.2015.02.1121","article-title":"Assessment of rosacea severity: A review of evaluation methods used in clinical trials","volume":"73","author":"Hopkinson","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.jaad.2014.08.028","article-title":"Rosacea: Part I. Introduction, categorization, histology, pathogenesis, and risk factors","volume":"72","author":"Two","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3109\/15569527.2014.930749","article-title":"Rosacea-the ophthalmic perspective","volume":"34","author":"Awais","year":"2015","journal-title":"Cutan. Ocul. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.jaad.2016.01.023","article-title":"Improved clinical outcome and biomarkers in adults with papulopustular rosacea treated with doxycycline modified-release capsules in a randomized trial","volume":"74","author":"Holmes","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.jaad.2016.02.1158","article-title":"Assessment of the risk of cardiovascular disease in patients with rosacea","volume":"75","author":"Egeberg","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s13555-016-0168-8","article-title":"Acne and Rosacea","volume":"7","author":"Picardo","year":"2017","journal-title":"Dermatol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jdermsci.2015.12.006","article-title":"The role of altered cutaneous immune responses in the induction and persistence of rosacea","volume":"82","author":"Margalit","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.jaad.2014.05.036","article-title":"The psychological impact of rosacea and the influence of current management options","volume":"71","author":"Moustafa","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jdds.2015.04.003","article-title":"Psychological disorders associated with rosacea: Analysis of unscripted comments","volume":"19","author":"Cardwell","year":"2015","journal-title":"J. Dermatol. Dermatol. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.jaad.2015.07.009","article-title":"Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: Results of a case-control study","volume":"73","author":"Rainer","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.dsi.2017.03.006","article-title":"Assessment of Framingham risk score and systemic coronary risk evaluation in rosacea patients","volume":"35","author":"Altun","year":"2017","journal-title":"Dermatol. Sin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jaad.2015.04.028","article-title":"Cardiovascular comorbidities in patients with rosacea: A nationwide case-control study from Taiwan","volume":"73","author":"Hua","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.canep.2017.01.006","article-title":"Rosacea and risk of cancer in Denmark","volume":"47","author":"Egeberg","year":"2017","journal-title":"Cancer Epidemiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.clindermatol.2013.05.024","article-title":"Rosacea and rhinophyma","volume":"32","author":"Tuzun","year":"2014","journal-title":"Clin. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Woo, Y.R., Lim, J.H., Cho, D.H., and Park, H.J. (2016). Rosacea: Molecular Mechanisms and Management of a Chronic Cutaneous Inflammatory Condition. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091562"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nri.2015.8","article-title":"Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease","volume":"16","author":"Cao","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1016\/j.jaad.2013.04.045","article-title":"New insights into rosacea pathophysiology: A review of recent findings","volume":"69","author":"Steinhoff","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1038\/jid.2015.141","article-title":"Molecular and Morphological Characterization of Inflammatory Infiltrate in Rosacea Reveals Activation of Th1\/Th17 Pathways","volume":"135","author":"Buhl","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/bjd.15122","article-title":"Updating the diagnosis, classification and assessment of rosacea: Recommendations from the global ROSacea COnsensus (ROSCO) panel","volume":"176","author":"Tan","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.jaad.2014.08.027","article-title":"Rosacea: Part II. Topical and systemic therapies in the treatment of rosacea","volume":"72","author":"Two","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_24","first-page":"1","article-title":"Rosacea: An Update on Medical Therapies","volume":"19","author":"Chang","year":"2014","journal-title":"Skin Ther. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.clindermatol.2016.10.016","article-title":"Pharmacologic treatments for rosacea","volume":"35","author":"Layton","year":"2017","journal-title":"Clin. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/exd.13143","article-title":"Integrative concepts of rosacea pathophysiology, clinical presentation and new therapeutics","volume":"26","author":"Holmes","year":"2017","journal-title":"Exp. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1080\/09546634.2017.1343435","article-title":"Defining treatment success in rosacea as \u2018clear\u2019 may provide multiple patient benefits: Results of a pooled analysis","volume":"28","author":"Webster","year":"2017","journal-title":"J. Dermatol. Treat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.dsi.2015.04.012","article-title":"Topical tranexamic acid improves the permeability barrier in rosacea","volume":"33","author":"Zhong","year":"2015","journal-title":"Dermatol. Sin."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sun, H., Zhu, X., Cai, W., and Qiu, L. (2017). Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-\u03b3 Dependent on PI3K\/Akt\/mTOR Signal Pathway. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040844"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Park, H.J., Park, H.S., Lee, J.U., Bothwell, A.L., and Choi, J.M. (2016). Sex-Based Selectivity of PPAR\u03b3 Regulation in Th1, Th2, and Th17 Differentiation. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17081347"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12213","DOI":"10.3390\/ijms160612213","article-title":"Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL\/6J Mice","volume":"16","author":"Jia","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"709","DOI":"10.3797\/scipharm.1407-16","article-title":"Pioglitazone and Endothelial Dysfunction: Pleiotropic Effects and Possible Therapeutic Implications","volume":"82","author":"Radenkovic","year":"2014","journal-title":"Sci. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.saa.2017.03.028","article-title":"Simultaneous spectrophotometric determination of glimepiride and pioglitazone in binary mixture and combined dosage form using chemometric-assisted techniques","volume":"182","author":"Elkady","year":"2017","journal-title":"Spectrochim. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Suzuki, S., Mori, Y., Nagano, A., Naiki-Ito, A., Kato, H., Nagayasu, Y., Kobayashi, M., Kuno, T., and Takahashi, S. (2016). Pioglitazone, a Peroxisome Proliferator-Activated Receptor \u03b3 Agonist, Suppresses Rat Prostate Carcinogenesis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122071"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jconrel.2014.12.006","article-title":"Peptides as skin penetration enhancers: Mechanisms of action","volume":"199","author":"Kumar","year":"2015","journal-title":"J. Controll. Release"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.saa.2017.05.026","article-title":"Elucidation of penetration enhancement mechanism of Emu oil using FTIR microspectroscopy at EMIRA laboratory of SESAME synchrotron","volume":"185","author":"Mansour","year":"2017","journal-title":"Spectrochim. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ijpharm.2016.05.004","article-title":"Transdermal permeation of drugs with differing lipophilicity: Effect of penetration enhancer camphor","volume":"507","author":"Xie","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.intimp.2016.09.028","article-title":"PPAR-gamma agonist pioglitazone regulates dendritic cells immunogenicity mediated by DC-SIGN via the MAPK and NF-\u03baB pathways","volume":"41","author":"Zhu","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3109\/10799893.2016.1171341","article-title":"Pioglitazone inhibits growth of human retinoblastoma cells via regulation of NF-\u03baB inflammation signals","volume":"37","author":"Wang","year":"2017","journal-title":"J. Recept. Signal Transduct. Res."},{"key":"ref_40","first-page":"70","article-title":"HPLC method development, validation and its application to investigate in vitro effect of pioglitazone on the availability of H 1 receptor antagonists","volume":"22","author":"Mirza","year":"2017","journal-title":"J. Assoc. Arab Univ. Basic Appl. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jpha.2014.02.002","article-title":"Pioglitazone: A review of analytical methods","volume":"4","author":"Satheeshkumar","year":"2014","journal-title":"J. Pharm. Anal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1080\/03007995.2017.1352497","article-title":"Skin penetration and tissue permeation after topical administration of diclofenac","volume":"33","author":"Hagen","year":"2017","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/14764172.2016.1247965","article-title":"Skin permeation and retention of topical bead formulation containing tranexamic acid","volume":"19","author":"Vijayakumar","year":"2017","journal-title":"J. Cosmet. Laser Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0378-5173(94)90098-1","article-title":"Effect of d-limonene on the transdermal permeation of nifedipine and domperidone","volume":"103","author":"Calpena","year":"1994","journal-title":"Int. J. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1208\/s12248-014-9646-z","article-title":"Effect of excipients on the particle size of precipitated pioglitazone in the gastrointestinal tract: Impact on bioequivalence","volume":"16","author":"Sugita","year":"2014","journal-title":"AAPS J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/10837450801949350","article-title":"Studies on optimizing in vitro transdermal permeation of ondansetron hydrochloride using nerodilol, carvone, and limonene as penetration enhancers","volume":"13","author":"Krishnaiah","year":"2008","journal-title":"Pharm. Dev. Technol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1080\/13880209.2017.1312464","article-title":"Development of essential oils as skin permeation enhancers: Penetration enhancement effect and mechanism of action","volume":"55","author":"Jiang","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ijpharm.2013.02.048","article-title":"Enhancement of skin permeation of bufalin by limonene via reservoir type transdermal patch: Formulation design and biopharmaceutical evaluation","volume":"447","author":"Yang","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2174\/18715230113126660021","article-title":"Skin Repair Properties of d-Limonene and Perillyl Alcohol in Murine Models","volume":"13","author":"Mirshahi","year":"2014","journal-title":"Anti-Inflamm. Anti-Allergy Agents Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/cod.12287","article-title":"Occupational contact dermatitis caused by d-limonene","volume":"71","author":"Pesonen","year":"2014","journal-title":"Contact Dermat."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1600-0536.2006.00930.x","article-title":"Identification and classification of skin sensitizers: Identifying false positives and false negatives","volume":"55","author":"Basketter","year":"2006","journal-title":"Contact Dermat."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1080\/10937404.2013.769418","article-title":"Safety evaluation and risk assessment of d-Limonene","volume":"16","author":"Kim","year":"2013","journal-title":"J. Toxicol. Environ. Health Part B"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.ultsonch.2013.10.013","article-title":"Skin permeation of d-limonene-based nanoemulsions as a transdermal carrier prepared by ultrasonic emulsification","volume":"21","author":"Lu","year":"2014","journal-title":"Ultrason. Sonochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1177\/1091581813479979","article-title":"The fate of dermally applied [14C]d-limonene in rats and humans","volume":"32","author":"Api","year":"2013","journal-title":"Int. J. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1194\/jlr.R800001-JLR200","article-title":"Thematic review series: Skin lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology","volume":"49","author":"Schmuth","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.biomaterials.2016.05.001","article-title":"Redox nanoparticle increases the chemotherapeutic efficiency of pioglitazone and suppresses its toxic side effects","volume":"99","author":"Thangavel","year":"2016","journal-title":"Biomaterials"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"415","DOI":"10.5650\/jos.59.415","article-title":"Limonene suppresses lipopolysaccharide-induced production of nitric oxide, prostaglandin E2, and pro-inflammatory cytokines in RAW 264.7 macrophages","volume":"59","author":"Yoon","year":"2010","journal-title":"J Oleo Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ijpharm.2016.01.056","article-title":"Ex vivo permeation of carprofen from nanoparticles: A comprehensive study through human, porcine and bovine skin as anti-inflammatory agent","volume":"501","author":"Parra","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.3109\/10717544.2014.936536","article-title":"QbD-based carbopol transgel formulation: Characterization, pharmacokinetic assessment and therapeutic efficacy in diabetes","volume":"23","author":"Prasad","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_60","first-page":"3927","article-title":"Permeation studies of pioglitazone HCl from ficus carica fruit mucilage matrix transdermal Patches","volume":"3","author":"Rangari","year":"2012","journal-title":"IJPSR"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/jid.2013.448","article-title":"Preclinical studies of a specific PPAR\u03b3 modulator in the control of skin inflammation","volume":"134","author":"Mastrofrancesco","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3109\/03639049409038325","article-title":"Limonene and Related Compounds as Potential Skin Penetration Promoters","volume":"20","author":"Takayama","year":"2008","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.tice.2015.01.003","article-title":"The possible protective effect of simvastatin and pioglitazone separately and in combination on bleomycin-induced changes in mice thin skin","volume":"47","author":"Kandeel","year":"2015","journal-title":"Tissue Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cellimm.2012.09.002","article-title":"d-Limonene modulates T lymphocyte activity and viability","volume":"279","author":"Lappas","year":"2012","journal-title":"Cell. Immunol."},{"key":"ref_65","first-page":"2116","article-title":"The Pharmacokinetics of Pioglitazone in Thai Healthy Subjects","volume":"89","author":"Wittayalertpanya","year":"2006","journal-title":"J. Med. Assoc. Thail."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0022-3565(25)08751-8","article-title":"Methods for the study of irritation and toxcicity of substances applied topically to the skin and mucous membranes","volume":"82","author":"Draize","year":"1994","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/open.201700040","article-title":"Cationic Supramolecular Hydrogels for Overcoming the Skin Barrier in Drug Delivery","volume":"6","author":"Rodrigues","year":"2017","journal-title":"ChemistryOpen"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/12\/2548\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:51:35Z","timestamp":1760208695000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/12\/2548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,28]]},"references-count":67,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["ijms18122548"],"URL":"https:\/\/doi.org\/10.3390\/ijms18122548","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,28]]}}}