{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:35:14Z","timestamp":1786541714068,"version":"build-2736575974"},"reference-count":72,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Retinol, a bioactive small molecule of the vitamin A family, contributes epidermal and dermal tissue repair through retinoic acid receptor \u03b3 (RAR\u03b3)\/retinoid X receptor (RXR) receptor-mediated transcriptional regulation of keratinocyte differentiation, extracellular matrix (ECM) remodeling, and barrier restoration. However, the relationship between applied concentration, tissue-level regenerative outcomes, and tolerability remains incompletely characterized. This prospective, randomized, single-blind study compared biophysical effects and tolerance of two retinol concentrations in EU-compliant facial creams, high-performance liquid chromatography (HPLC)-verified as 0.104% and 0.247% (w\/w). Thirty-eight women aged 40\u201361 years (Fitzpatrick phototypes II\u2013III) participated across three independent sub-studies: 28 were randomized to either concentration for 12 weeks; 5 underwent split-face ultrasound imaging (0.247% versus retinol-free control) for 8 weeks; and 5 participated in a tape stripping sub-study quantifying stratum corneum interleukin-1 alpha (IL-1\u03b1) and interleukin-1 receptor antagonist (IL-1ra) by ELISA before and after 6 weeks of 0.247% retinol treatment. Main cohort assessments included transepidermal water loss (TEWL), hydration, melanin, erythema, pH, sebum, biomechanical parameters, and wrinkle grading. Both concentrations significantly improved barrier parameters\u2014hydration, TEWL, brightness, pH, and sebum\u2014with no inter-group differences. In the ultrasound sub-group, 0.247% retinol increased epidermal thickness (+12.4 \u03bcm), epidermal density (+3.84%), and dermal density (+1.81%) versus control, consistent with ECM reorganization and epidermal stratification. Biomechanical parameters showed no significant changes, consistent with retinol\u2019s remodeling timeline. Consumer assessment indicated comparable efficacy; 0.247% demonstrated superior smoothing but higher erythema incidence. In the tape stripping sub-study, IL-1\u03b1 decreased in all participants (median: 25.1 \u2192 13.2 picograms per tape [pg\/Tape]; 5\/5 concordant), while IL-1ra increased in 4\/5 participants (median: 352.8 \u2192 1403.1 picograms per three sequential tapes [pg\/3sT]), indicating a directionally consistent shift in the IL-1\u03b1\/IL-1ra balance; these results are exploratory and require replication in larger cohorts. These findings collectively support clinically meaningful barrier restoration and structural remodeling within current EU safety limits (Commission Regulation EU 2024\/996), with 0.104% offering a favorable efficacy-to-tolerability profile for initial therapy.<\/jats:p>","DOI":"10.3390\/ijms27167205","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:53:48Z","timestamp":1786539228000},"page":"7205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Barrier Function and Biophysical Effects of 0.104% and 0.247% Retinol Creams in Mature Facial Skin: A Prospective Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8947-9999","authenticated-orcid":false,"given":"Iwona","family":"Pord\u0105b","sequence":"first","affiliation":[{"name":"Department and Division of Practical Cosmetology and Skin Diseases Prophylaxis, Faculty of Pharmacy, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3448-5517","authenticated-orcid":false,"given":"Julia","family":"Cie\u015blawska","sequence":"additional","affiliation":[{"name":"Department and Division of Practical Cosmetology and Skin Diseases Prophylaxis, Faculty of Pharmacy, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9254-3728","authenticated-orcid":false,"given":"Micha\u0142","family":"Gackowski","sequence":"additional","affiliation":[{"name":"Doctoral School, Poznan University of Medical Sciences, 70 Bukowska Street, 60-812 Pozna\u0144, Poland"},{"name":"Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9295-7349","authenticated-orcid":false,"given":"Micha\u0142 J.","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Poznan University of Medical Sciences, 49 Przybyszewskiego Street, 60-355 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Paw\u0142owska","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Faculty of Chemistry, Adam Mickiewicz University, 8 Uniwersytetu Pozna\u0144skiego Street, 61-614 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3106-064X","authenticated-orcid":false,"given":"Justyna","family":"Gornowicz-Porowska","sequence":"additional","affiliation":[{"name":"Department and Division of Practical Cosmetology and Skin Diseases Prophylaxis, Faculty of Pharmacy, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6939-2888","authenticated-orcid":false,"given":"Tomasz","family":"Osma\u0142ek","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1482-8274","authenticated-orcid":false,"given":"Marta","family":"Marzec","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Faculty of Chemistry, Adam Mickiewicz University, 8 Uniwersytetu Pozna\u0144skiego Street, 61-614 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1113-9011","authenticated-orcid":false,"given":"Izabela","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Faculty of Chemistry, Adam Mickiewicz University, 8 Uniwersytetu Pozna\u0144skiego Street, 61-614 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9344-2822","authenticated-orcid":false,"given":"Anna","family":"Kroma-Szal","sequence":"additional","affiliation":[{"name":"Department and Division of Practical Cosmetology and Skin Diseases Prophylaxis, Faculty of Pharmacy, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariola","family":"Pawlaczyk","sequence":"additional","affiliation":[{"name":"Department and Division of Practical Cosmetology and Skin Diseases 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Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Boraldi, F., Lofaro, F.D., Bonacorsi, S., Mazzilli, A., Garcia-Fernandez, M., and Quaglino, D. (2024). The Role of Fibroblasts in Skin Homeostasis and Repair. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071586"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"El-Serafi, A.T., El-Serafi, I., Steinvall, I., Sj\u00f6berg, F., and Elmasry, M. (2022). A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147934"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/0190-9622(90)70265-J","article-title":"Sustained Improvement with Prolonged Topical Tretinoin (Retinoic Acid) for Photoaged Skin","volume":"23","author":"Ellis","year":"1990","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2147\/ciia.2006.1.4.327","article-title":"Retinoids in the Treatment of Skin Aging: An Overview of Clinical Efficacy and Safety","volume":"1","author":"Mukherjee","year":"2006","journal-title":"Clin. Interv. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e003","DOI":"10.1097\/JW9.0000000000000003","article-title":"Topical Tretinoin for Treating Photoaging: A Systematic Review of Randomized Controlled Trials","volume":"8","author":"Sitohang","year":"2022","journal-title":"Int. J. Women\u2019s Dermatol."},{"key":"ref_7","first-page":"100468","article-title":"Research Progress of Penetration Enhancers in Transdermal Drug Delivery Systems: Multidimensional Exploration from Mechanisms to Clinical Application","volume":"10","author":"Liu","year":"2025","journal-title":"Int. J. Pharm. X"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e70001","DOI":"10.1002\/bmm2.70001","article-title":"Innovative Transdermal Drug Delivery Systems: Benefits, Challenges, and Emerging Application","volume":"3","author":"Shah","year":"2025","journal-title":"BMEMat"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.35702\/Derm.10030","article-title":"Skin Based Delivery Systems for Therapeutic Molecules: Advancing Dermatological Treatments through Innovative Drug Delivery Technologies","volume":"5","author":"Owsley","year":"2025","journal-title":"Dermis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/ics.13013","article-title":"Cosmetic Retinoid Use in Photoaged Skin: A Review of the Compounds, Their Use and Mechanisms of Action","volume":"47","author":"Mambwe","year":"2024","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Szyma\u0144ski, \u0141., Skopek, R., Palusi\u0144ska, M., Schenk, T., Stengel, S., Lewicki, S., Kraj, L., Kami\u0144ski, P., and Zelent, A. (2020). Retinoic Acid and Its Derivatives in Skin. Cells, 9.","DOI":"10.3390\/cells9122660"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"\u0141uczak, J.W., Palusi\u0144ska, M., Ma\u015bli\u0144ska-Gromadka, K., Pietrzak, D., Szopi\u0144ski, T., Lewicki, S., Schenk, T., and Szyma\u0144ski, \u0141. (2025). The Next Generation of Skin Care: Transforming Retinoid Therapeutics. Cells, 14.","DOI":"10.3390\/cells14211650"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, K., Yang, Z., Ma, Y., Liu, W., Li, G., Xu, X., and Li, Q. (2025). Retinoids in Scarless Skin Regeneration: From Molecular Mechanisms to Therapeutic Strategies. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1683851"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/ics.12348","article-title":"Molecular Basis of Retinol Anti-Ageing Properties in Naturally Aged Human Skin In Vivo","volume":"39","author":"Shao","year":"2017","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Quan, T. (2023). Human Skin Aging and the Anti-Aging Properties of Retinol. Biomolecules, 13.","DOI":"10.3390\/biom13111614"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"392","DOI":"10.5114\/ada.2019.87443","article-title":"Retinoids: Active Molecules Influencing Skin Structure Formation in Cosmetic and Dermatological Treatments","volume":"36","author":"Zasada","year":"2019","journal-title":"Adv. Dermatol. Allergol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e194188","DOI":"10.1172\/jci.insight.194188","article-title":"A Multiomics Analysis Identifies Retinol Metabolism in Fibroblasts as a Key Pathway in Wound Healing","volume":"10","author":"Madzharova","year":"2025","journal-title":"JCI Insight"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106784","DOI":"10.1016\/j.ejps.2024.106784","article-title":"Spectral and Mass Characterization of Kinetic Conversion from Retinoids to Retinoic Acid in an In Vitro 3-D Human Skin Equivalent Model","volume":"198","author":"Kim","year":"2024","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1111\/exd.14781","article-title":"Bioconversion of Retinol and Its Cell Barrier Function in Human Immortalized Keratinocytes Cells and Artificial Epidermis-Dermis Skin","volume":"32","author":"Kim","year":"2023","journal-title":"Exp. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10558","DOI":"10.1038\/s41598-023-37750-5","article-title":"One-Year Longitudinal Study of the Stratum Corneum Proteome of Retinol and All-Trans-Retinoic Acid Treated Human Skin: An Orchestrated Molecular Event","volume":"13","author":"Abed","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_21","first-page":"1789","article-title":"All-Trans Retinoic Acid Alters the Expression of the Tight Junction Proteins Claudin-1 and -4 and Epidermal Barrier Function-Associated Genes in the Epidermis","volume":"43","author":"Li","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/jocd.12193","article-title":"A Comparative Study of the Effects of Retinol and Retinoic Acid on Histological, Molecular, and Clinical Properties of Human Skin","volume":"15","author":"Kong","year":"2016","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/1523-1747.ep12343819","article-title":"Hyaluronic Acid and Dermatan Sulfate Are Selectively Stimulated by Retinoic Acid in Irradiated and Nonirradiated Hairless Mouse Skin","volume":"106","author":"Margelin","year":"1996","journal-title":"J. Investig. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2298\/ABS220215007C","article-title":"Retinoic acid induces hyaluronic acid production through the klotho-mediated EGFR signaling pathway in human epidermal keratinocytes","volume":"74","author":"Choi","year":"2022","journal-title":"Arch. Biol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"203","DOI":"10.4062\/biomolther.2022.001","article-title":"Loss of EMP2 Inhibits Melanogenesis of MNT1 Melanoma Cells via Regulation of TRP-2","volume":"30","author":"Enkhtaivan","year":"2022","journal-title":"Biomol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"He, X., Gao, X., and Xie, W. (2024). Research Progress in Skin Aging and Immunity. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25074101"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Qian, H., Shan, Y., Gong, R., Lin, D., Zhang, M., Wang, C., and Wang, L. (2023). Mechanism of Action and Therapeutic Effects of Oxidative Stress and Stem Cell-Based Materials in Skin Aging: Current Evidence and Future Perspectives. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1082403"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3793\/jaam.8.23","article-title":"Glycation Stress and Photo-Aging in Skin","volume":"8","author":"Ichihashi","year":"2011","journal-title":"Anti-Aging Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.clindermatol.2019.04.005","article-title":"Skin Aging: The Dermal Perspective","volume":"37","author":"Strnadova","year":"2019","journal-title":"Clin. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00403-024-02908-2","article-title":"Cosmeceuticals for Antiaging: A Systematic Review of Safety and Efficacy","volume":"316","author":"Lau","year":"2024","journal-title":"Arch. Dermatol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e156344","DOI":"10.1172\/jci.insight.156344","article-title":"UVB-Mediated DNA Damage Induces Matrix Metalloproteinases to Promote Photoaging in an AhR- and SP1-Dependent Manner","volume":"7","author":"Kim","year":"2022","journal-title":"JCI Insight"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s13671-020-00288-0","article-title":"Photoaging: A Review of Current Literature","volume":"9","author":"Huang","year":"2020","journal-title":"Curr. Dermatol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1600-0625.1998.tb00299.x","article-title":"In Vitro Metabolism by Human Skin and Fibroblasts of Retinol, Retinal and Retinoic Acid","volume":"7","author":"Bailly","year":"1998","journal-title":"Exp. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"209","DOI":"10.36849\/JDD.8124","article-title":"Efficacy and Tolerability of Topical 0.1% Stabilized Bioactive Retinol for Photoaging: A Vehicle-Controlled Integrated Analysis","volume":"23","author":"Farris","year":"2024","journal-title":"J. Drugs Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/ics.12799","article-title":"Multifaceted amelioration of cutaneous photoageing by (0.3%) retinol","volume":"44","author":"Mellody","year":"2022","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_36","unstructured":"European Commission, and Scientific Committee on Consumer Safety (SCCS) (2024). Revision of the Scientific Opinion on Vitamin A (Retinol, Retinyl Acetate, Retinyl Palmitate), Publications Office of the European Union. Available online: https:\/\/health.ec.europa.eu\/publications\/revision-scientific-opinion-sccs157616-vitamin-retinol-retinyl-acetate-retinyl-palmitate_en."},{"key":"ref_37","unstructured":"European Commission (2024). Commission Regulation (EU) 2024\/996 of 3 April 2024 Amending Regulation (EC) No 1223\/2009 of the European Parliament and of the Council as Regards the Use of Vitamin A, Alpha-Arbutin and Arbutin and Certain Substances with Potential Endocrine Disrupting Properties in Cosmetic Products. Off. J. Eur. Union, 2024\/996, Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX:32024R0996."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1111\/jocd.16330","article-title":"Mitigation of Retinol-Induced Skin Irritation by Physiologic Lipids: Evidence from Patch Testing","volume":"23","author":"Fang","year":"2024","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_39","first-page":"665","article-title":"Safety of Skin Care Products during Pregnancy","volume":"57","author":"Bozzo","year":"2011","journal-title":"Can. Fam. Physician"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Macleod, T., Berekmeri, A., Bridgewood, C., Stacey, M., McGonagle, D., and Wittmann, M. (2021). The Immunological Impact of IL-1 Family Cytokines on the Epidermal Barrier. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.808012"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1600-0625.1998.tb00332.x","article-title":"An increased ratio of interleukin-1 receptor antagonist to interleukin-1alpha in inflammatory skin diseases","volume":"7","author":"Terui","year":"1998","journal-title":"Exp. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/bjd.19760","article-title":"Tape strips in dermatology research","volume":"185","author":"Hughes","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.2340\/00015555-2709","article-title":"Minimally-invasive sampling of interleukin-1\u03b1 and interleukin-1 receptor antagonist from the skin: A systematic review of in vivo studies in humans","volume":"97","author":"Falcone","year":"2017","journal-title":"Acta Derm. Venereol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1093\/bjd\/ljaf275","article-title":"Tape strips in inflammatory skin disease: A noninvasive method for molecular insights and personalized care","volume":"193","author":"Liu","year":"2025","journal-title":"Br. J. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1111\/jocd.13686","article-title":"Quality Control of Retinoids in Commercial Cosmetic Products","volume":"20","author":"Kristl","year":"2021","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"108","DOI":"10.22159\/ijap.2024v16i4.50903","article-title":"Retinol Stability in Anti-Aging Face Serum Post-Opening Period","volume":"16","author":"Maggadani","year":"2024","journal-title":"Int. J. Appl. Pharm."},{"key":"ref_47","unstructured":"Bazin, R., and Doublet, E. (2007). Skin Aging Atlas, Volume 1: Caucasian Type, Med\u2019Com."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1159\/000094670","article-title":"The PH of the Skin Surface and Its Impact on the Barrier Function","volume":"19","author":"Korting","year":"2006","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1159\/000231524","article-title":"Variation of Skin Surface PH, Sebum Content and Stratum Corneum Hydration with Age and Gender in a Large Chinese Population","volume":"22","author":"Man","year":"2009","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Luki\u0107, M., Panteli\u0107, I., and Savi\u0107, S.D. (2021). Towards Optimal pH of the Skin and Topical Formulations: From the Current State of the Art to Tailored Products. Cosmetics, 8.","DOI":"10.3390\/cosmetics8030069"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Pequeno, A.L.V., and Bagatin, E. (2024). Dermatological Ultrasound in Assessing Skin Aging. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1353605"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"535","DOI":"10.5114\/ada.2017.72457","article-title":"Current Applications of High-Frequency Ultrasonography in Dermatology","volume":"34","author":"Zaba","year":"2017","journal-title":"Adv. Dermatol. Allergol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1111\/exd.13675","article-title":"Topical Retinol Attenuates Stress-Induced Ageing Signs in Human Skin Ex Vivo, Through EGFR Activation via EGF, but Not ERK and AP-1 Activation","volume":"28","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_54","first-page":"955","article-title":"Anti-Aging Effects of Hippophae rhamnoides Emulsion on Human Skin","volume":"11","author":"Khan","year":"2013","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Boo, Y. (2022). Ascorbic Acid (Vitamin C) as a Cosmeceutical to Increase Dermal Collagen for Skin Antiaging Purposes: Emerging Combination Therapies. Antioxidants, 11.","DOI":"10.3390\/antiox11091663"},{"key":"ref_56","unstructured":"Cosmetic Ingredient Review (CIR) (2020). Safety Assessment of Ascorbyl Glucoside and Sodium Ascorbyl Glucoside as Used in Cosmetics, Cosmetic Ingredient Review. Available online: https:\/\/www.cir-safety.org\/sites\/default\/files\/ascorb092020FR.pdf."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Fenini, G., Contassot, E., and French, L.E. (2017). Potential of IL-1, IL-18 and inflammasome inhibition for the treatment of inflammatory skin diseases. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00278"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10472","DOI":"10.1038\/srep10472","article-title":"Age-dependent variation in cytokines, chemokines, and biologic analytes rinsed from the surface of healthy human skin","volume":"5","author":"Kinn","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1034\/j.1600-0625.2002.110303.x","article-title":"Alterations in cytokine regulation in aged epidermis: Implications for permeability barrier homeostasis and inflammation","volume":"11","author":"Ye","year":"2002","journal-title":"Exp. Dermatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/phpp.12743","article-title":"Bioactive substances in the stratum corneum of the epidermis found as indicators of skin damage due to sun exposure","volume":"38","author":"Fukunaga","year":"2022","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1111\/1523-1747.ep12340143","article-title":"Elevation of interleukin 1 receptor antagonist in the stratum corneum of sun-exposed and ultraviolet B-irradiated human skin","volume":"106","author":"Hirao","year":"1996","journal-title":"J. Investig. Dermatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"417","DOI":"10.4062\/biomolther.2017.167","article-title":"IL-1 receptor antagonist reduced chemical-induced keratinocyte apoptosis through antagonism to IL-1\u03b1\/IL-1\u03b2","volume":"26","author":"Lee","year":"2018","journal-title":"Biomol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1159\/000508168","article-title":"A Clinical Anti-Ageing Comparative Study of 0.3 and 0.5% Retinol Serums: A Clinically Controlled Trial","volume":"33","author":"Zasada","year":"2020","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1111\/jocd.13286","article-title":"An Evaluation of the Physicochemical Parameters and the Content of the Active Ingredients in Original Formulas Containing Retinol","volume":"19","author":"Zasada","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/jocd.13040","article-title":"Randomized Parallel Control Trial Checking the Efficacy and Impact of Two Concentrations of Retinol in the Original Formula on the Aging Skin Condition: Pilot Study","volume":"19","author":"Zasada","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_66","first-page":"1323","article-title":"A Long Term Study of the Difference in Efficacy and Effect Rate of Various Concentrations of Retinol (1500\u20136600 IU) in Middle Aged Women","volume":"315","author":"Jang","year":"2023","journal-title":"Arch. Dermatol. Res."},{"key":"ref_67","first-page":"271","article-title":"One-Year Topical Stabilized Retinol Treatment Improves Photodamaged Skin in a Double-Blind, Vehicle-Controlled Trial","volume":"14","author":"Randhawa","year":"2015","journal-title":"J. Drugs Dermatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2165\/00128071-200506040-00005","article-title":"Long-Term Efficacy and Safety of Tretinoin Emollient Cream 0.05% in the Treatment of Photodamaged Facial Skin: A Two-Year, Randomized, Placebo-Controlled Trial","volume":"6","author":"Kang","year":"2005","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Martin, P., Goldstein, J., Mermoud, L., D\u00edaz-Barreiro, A., and Palmer, G. (2021). IL-1 family antagonists in mouse and human skin inflammation. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.652846"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Paw\u0142owska, M., Marzec, M., Jankowiak, W., and Nowak, I. (2024). Solid Lipid Nanoparticles Incorporated with Retinol and Pentapeptide-18\u2014Optimization, Characterization, and Cosmetic Application. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810078"},{"key":"ref_71","unstructured":"Courage + Khazaka Electronic GmbH (2024, February 18). Scientific Products for Skin Testing. Available online: https:\/\/www.courage-khazaka.com\/en\/scientific-products\/all-products."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1111\/j.1365-2133.2004.06084.x","article-title":"Stratum corneum adhesive tape stripping: Influence of anatomical site, application pressure, duration and removal","volume":"151","author":"Dreher","year":"2004","journal-title":"Br. J. Dermatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7205\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:54:57Z","timestamp":1786539297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":72,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167205"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167205","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]}}}