{"title":"RP-18 TLC and Computational Descriptors of Skin Permeability of Sunscreens.","authors":"Anna W Sobańska, Elżbieta Brzezińska","doi":"10.1159/000522366","DOIUrl":"https://doi.org/10.1159/000522366","url":null,"abstract":"<p><p>The relationships between the reversed-phase thin layer chromatographic retention parameters obtained on octadecyl-modified silica (RP-18) sorbent for mobile phases containing water and one of six water-miscible organic modifiers (acetone, methanol, acetonitrile, tetrahydrofurane, N,N-dimethylformamide, 1,4-dioxane) and skin permeability coefficients were studied for a group of 21 cosmetic raw materials, mainly organic sunscreens and preservatives. The correlations between the skin permeability coefficients log Kd calculated in silico using EpiSuite software and the RP-18 thin layer chromatographic retention parameters are mostly linear, especially for compounds of lower-to-medium lipophilicity. It was established that skin permeability coefficient models based on retention parameters collected for mobile phases containing acetone or dioxane (75% v/v), proposed for structurally unrelated cosmetic raw materials are also applicable to other actives, as shown using a test set of compounds whose in vivo log Kd data are available. Skin permeability models developed in this study have the benefit of being based on easily obtained, chromatographic descriptors and their applicability extends beyond cosmetic chemistry.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":"35 3","pages":"174-179"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39773514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sung Ha Lim, Eun Jung Kim, Chung Hyuk Lee, Gi Hyun Park, Kang Min Yoo, Sung Ju Nam, Kyong-Oh Shin, Kyungho Park, Eung Ho Choi
{"title":"A Lipid Mixture Enriched by Ceramide NP with Fatty Acids of Diverse Chain Lengths Contributes to Restore the Skin Barrier Function Impaired by Topical Corticosteroid.","authors":"Sung Ha Lim, Eun Jung Kim, Chung Hyuk Lee, Gi Hyun Park, Kang Min Yoo, Sung Ju Nam, Kyong-Oh Shin, Kyungho Park, Eung Ho Choi","doi":"10.1159/000518517","DOIUrl":"https://doi.org/10.1159/000518517","url":null,"abstract":"<p><strong>Introduction: </strong>The stratum corneum (SC) is a skin barrier that consists of corneocytes, intercellular lipids, and corneodesmosomes. Ceramides are composed of sphingoid bases linked with various types of fatty acids (FAs), and they are an essential constituent of SC intercellular lipids. Among their subtypes, ceramide NP with a phytosphingosine base is especially important. Most of the previous studies on barrier recovery have focused on a specific ceramide with a single chain FA, not with diverse chain lengths. Skin barrier function is impaired by various factors, including topical corticosteroid.</p><p><strong>Objective: </strong>We evaluated whether a lipid mixture enriched by ceramide NP with FAs of diverse chain lengths (CER [NP]*) can restore the skin barrier function impaired by topical corticosteroid.</p><p><strong>Methods: </strong>Twenty-seven healthy adult male volunteers were recruited. Topical corticosteroid was applied on both volar forearms of volunteers. Then, the test cream containing a lipid mixture with CER (NP)* was applied on the left forearm, and a vehicle cream without a lipid mixture was applied on the right forearm of each subject. The functional parameters of the skin barrier were compared before and after the treatment. Epidermal differentiation markers, hyaluronic acid synthase 3 (HAS3), cytokine levels, and the lipid profiles in the SC were analyzed.</p><p><strong>Results: </strong>The functional parameters of the skin barrier, such as barrier recovery rate, SC integrity, and SC hydration were significantly improved in the test cream-applied site compared to the vehicle cream-applied sites. Filaggrin and HAS3 levels were significantly higher in the sites applied with the test cream. Interleukin (IL)-1α levels were also significantly increased in these sites. IL-2, IL-6, IL-10, and IL-13 levels were significantly decreased in the test cream-applied sites. Lipid analyses showed that C18, C20, and total ceramide NP levels significantly increased in the sites where the test cream was applied. Also, C16, C18, C20, C24, and total ceramide NP levels were significantly elevated in the test cream-applied sites after acute barrier disruption.</p><p><strong>Conclusion: </strong>Our results demonstrate that a lipid mixture enriched by CER (NP)* could recover the barrier function impaired by topical corticosteroid.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":"35 2","pages":"112-123"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000518517","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9871164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lara Camillo, Elena Grossini, Serena Farruggio, Patrizia Marotta, Laura Cristina Gironi, Elisa Zavattaro, Paola Savoia
{"title":"Alpha-Tocopherol Protects Human Dermal Fibroblasts by Modulating Nitric Oxide Release, Mitochondrial Function, Redox Status, and Inflammation.","authors":"Lara Camillo, Elena Grossini, Serena Farruggio, Patrizia Marotta, Laura Cristina Gironi, Elisa Zavattaro, Paola Savoia","doi":"10.1159/000517204","DOIUrl":"https://doi.org/10.1159/000517204","url":null,"abstract":"<p><strong>Background: </strong>The altered balance between oxidants/antioxidants and inflammation, changes in nitric oxide (NO) release, and mitochondrial function have a role in skin aging through fibroblast modulation. Tocopherol is promising in counteracting the abovementioned events, but the effective mechanism of action needs to be clarified.</p><p><strong>Objective: </strong>The aim of this study was to examine the effects of α-tocopherol on cell viability/proliferation, NO release, mitochondrial function, oxidants/antioxidants, and inflammation in human dermal fibroblasts (HDF) subjected to oxidative stress.</p><p><strong>Methods: </strong>HDF were treated with H2O2 in the presence or absence of 1-10 μM α-tocopherol. Cell viability, reactive oxygen species (ROS), NO release, and mitochondrial membrane potential were measured; glutathione (GSH), superoxide dismutase (SOD)-1 and -2, glutathione peroxidase-1 (GPX-1), inducible NO synthase (iNOS), and Ki-67 were evaluated by RT-PCR and immunofluorescence; cell cycle was analyzed using FACS. Pro- and anti-inflammatory cytokine gene expression was analyzed through qRT-PCR.</p><p><strong>Results: </strong>α-Tocopherol counteracts H2O2, although it remains unclear whether this effect is dose dependent. Improvement of cell viability, mitochondrial membrane potential, Ki-67 expression, and G0/G1 and G2/M phases of the cell cycle was observed. These effects were accompanied by the increase of GSH content and the reduction of SOD-1 and -2, GPX-1, and ROS release. Also, iNOS expression and NO release were inhibited, and pro-inflammatory cytokine gene expression was decreased, confirming the putative role of α-tocopherol against inflammation.</p><p><strong>Conclusion: </strong>α-Tocopherol exerts protective effects in HDF which underwent oxidative stress by modulating the redox status, inflammation, iNOS-dependent NO release, and mitochondrial function. These observations have a potential role in the prevention and treatment of photoaging-related skin cancers.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":"35 1","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000517204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39164845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristýna Hergesell, Kateřina Valentová, Vladimír Velebný, Kateřina Vávrová, Iva Dolečková
{"title":"Common Cosmetic Compounds Can Reduce Air Pollution-Induced Oxidative Stress and Pro-Inflammatory Response in the Skin.","authors":"Kristýna Hergesell, Kateřina Valentová, Vladimír Velebný, Kateřina Vávrová, Iva Dolečková","doi":"10.1159/000522276","DOIUrl":"https://doi.org/10.1159/000522276","url":null,"abstract":"<p><strong>Introduction: </strong>Constantly increasing air pollution (AP) poses a concern affecting not only our health but also our skin. A typical manifestation of the skin damage induced by AP is its premature aging, irritation, skin barrier impairment, pigmentation disorders, and development or exacerbation of various skin diseases. For these reasons, it is crucial to protect the skin from the negative effects of AP. In this study, we evaluated the ability of some compounds commonly used in dermatological or cosmetic preparations with various biological activities to reduce AP-induced skin damage.</p><p><strong>Methods: </strong>We established a new experimental model using porcine skin explants exposed to cigarette smoke (CS) in which we determined the level of reactive oxygen species (ROS) in the stratum corneum, skin barrier lipids peroxidation, and gene expression of the pro-inflammatory cytokine interleukin 6 in the epidermis. Then, we tested several polysaccharides and their derivatives such as sodium hyaluronate (SH) of different molecular weight (MW, 1.6 MDa, 300 kDa, 15 kDa, 5 kDa), yeast glucomannan, schizophyllan, and carboxymethyl β-glucan, then vitamin C derivative sodium ascorbyl phosphate, niacinamide, and D-panthenol for their ability to prevent CS-induced skin damage. For the evaluation and comparison of their mechanism of action, film-forming effect was determined by TEWL and gloss measurements and the antioxidant properties were assessed by DPPH assay.</p><p><strong>Results: </strong>In the skin samples exposed to CS, we observed significant negative changes such as the presence of large amount of ROS in the stratum corneum, high level of skin barrier lipids peroxidation and upregulated IL6 gene expression. Pretreatment of the skin samples with all the tested substances significantly prevented CS-induced skin damage. The most effective were high MW SH probably due to its best film-forming effect and sodium ascorbyl phosphate with the best antioxidant properties.</p><p><strong>Conclusion: </strong>AP leads to a significant skin damage which can be effectively prevented using some conventional cosmetic and dermatological ingredients with various mechanisms of action.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":"35 3","pages":"156-165"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39737619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirjam J Schaap, Finola M Bruins, Noa Johanna Maria van den Brink, Kadri Orro, Hans M M Groenewoud, Elke M G J de Jong, Ellen H van den Bogaard, Marieke M B Seyger
{"title":"Challenges in Noninvasive Skin Biomarker Measurements in Daily Practice: A Longitudinal Study on Skin Surface Protein Detection by the Transdermal Analysis Patch in Pediatric Psoriasis.","authors":"Mirjam J Schaap, Finola M Bruins, Noa Johanna Maria van den Brink, Kadri Orro, Hans M M Groenewoud, Elke M G J de Jong, Ellen H van den Bogaard, Marieke M B Seyger","doi":"10.1159/000527258","DOIUrl":"https://doi.org/10.1159/000527258","url":null,"abstract":"<p><strong>Introduction: </strong>Skin surface proteins are potential biomarkers in psoriasis and can be measured noninvasively with the transdermal analysis patch (TAP). This study aimed to assess markers measured by TAP over time in daily clinical practice, explore their correlation with disease severity in pediatric psoriasis, and compare the TAP and tape stripping detection capability.</p><p><strong>Methods: </strong>In this prospective observational daily clinical practice study, pediatric psoriasis patients (aged >5 to <18 years) were followed during 1 year. At each visit, TAPs were applied to lesional (n = 2), peri-lesional (n = 2), and non-lesional (n = 1) sites. Post-lesional skin was sampled if all lesions on the arms, legs, or trunk cleared. Treatment and psoriasis severity data were collected. IL-1RA, hBD-2, IL-1α, IL-8, VEGF, CXCL-1/2, CCL-27, IL-23, hBD-1, IL-22, IL-17A, KLK-5, and IL-4 levels were quantified by spot-ELISA. For the statistical analysis, Wilcoxon signed rank tests, Mann-Whitney U tests, and Spearman correlations were used. Detection capability of the TAP was compared to tape stripping in a separate cohort of adult psoriasis patients.</p><p><strong>Results: </strong>32 patients (median age 15.0 years, median Psoriasis Area and Severity Index [PASI] 5.2) were followed for a mean of 11.3 (±3.4) months with a total of 104 visits. In lesional skin (n = 197), significantly higher IL-1RA, hBD-2, IL-8, VEGF, CXCL-1/2, IL-23, hBD-1, IL-22, CCL-27, and IL-17A levels were found compared to non-lesional skin (n = 104), while IL-1α was higher in non-lesional skin. Marker levels were highly variable over time and did not correlate with disease severity measured by PASI or SUM scores. Comparison of the TAP and tape strip detection capability in adult psoriasis patients (n = 10) showed that lesional hBD-2, IL1-α, IL-8, and VEGF and non-lesional IL-1RA, hBD-2, IL-8, and VEGF were more frequently detected in tape extracts than TAPs.</p><p><strong>Conclusion: </strong>Due to the lack of correlation with clinical disease severity and the current detection capability of the markers measured by TAP in psoriasis, its use in regular practice is still a bridge too far.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":"35 6","pages":"319-327"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10478167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sinomenine Suppressed Keratinocyte Proliferation and Imiquimod-Induced Psoriasis-Like Dermatitis by Regulating lncRNA XIST.","authors":"Shoubao Xiang, Xing Wu, Yu Xiang","doi":"10.1159/000526420","DOIUrl":"https://doi.org/10.1159/000526420","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic inflammatory skin disease. Sinomenine (SIN) has anti-inflammatory and antioxidant effects.</p><p><strong>Objective: </strong>The objective of this study was to confirm the anti-inflammatory effects and mechanism of SIN in imiquimod (IMQ)-induced psoriasis-like mouse model and IMQ-induced differentiated human keratinocytes (HaCaT) cells.</p><p><strong>Methods: </strong>BALB/c mice were treated with IMQ to construct a psoriasis-like mice model. PASI score and HE staining were used to observe pathology injury of skin tissue. The secretion of inflammatory factors and the oxidative stress level were detected by ELISA. HaCaT cells after induction of differentiation were treated with IMQ (100 μM) and SIN (10 μg/mL or 50 μg/mL), cell viability, the secretion of inflammatory factors, and the oxidative stress level were detected by MTT assay, ELISA, respectively. The expression of lncRNA XIST was detected by RT-qPCR. The relationship between XIST and EIF4G2 protein was detected by RNA immunoprecipitation (RIP) assay and ubiquitination experiment.</p><p><strong>Results: </strong>SIN significantly reduced PASI score, epidermal thickness, inflammatory response, and oxidative stress levels that increased by IMQ in vivo. SIN inhibited IMQ-induced HaCaT cell proliferation, inflammatory response, and oxidative stress levels and decreased the expression of XIST. Overexpression of XIST negated the protective effect of SIN on HaCaT cells. XIST interacted directly with EIF4G2 and regulated EIF4G2 expression via K48 ubiquitin. Knockdown of XIST reduced the half-life of EIF4G2 and decreased EIF4G2 protein stability. In addition, the E3 ubiquitin protein ligase MDM2 interacted with EIF4G2 and downregulated EIF4G2 expression. XIST reduced the interaction between MDM2 and EIF4G2, which mediated EIF4G2 K48 ubiquitination. Overexpression of XIST negated the protective effect of SIN on the inflammation of HaCaT cells through activating the NF-κB signaling pathway, while NF-κB pathway inhibitor PDTC reversed this result.</p><p><strong>Conclusion: </strong>SIN had a protective effect on psoriasis and could inhibit HaCaT cell proliferation and inflammatory response via XIST/MDM2/EIF4G2/NF-κB axis.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":"35 6","pages":"328-342"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10484538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maxim E Darvin, Johannes Schleusener, Jürgen Lademann, Chun-Sik Choe
{"title":"Current Views on Noninvasive in vivo Determination of Physiological Parameters of the Stratum Corneum Using Confocal Raman Microspectroscopy.","authors":"Maxim E Darvin, Johannes Schleusener, Jürgen Lademann, Chun-Sik Choe","doi":"10.1159/000521416","DOIUrl":"https://doi.org/10.1159/000521416","url":null,"abstract":"<p><p>Confocal Raman microspectroscopy is widely used in dermatology and cosmetology for analysis of the concentration of skin components (lipids, natural moisturizing factor molecules, water) and the penetration depth of cosmetic/medical formulations in the human stratum corneum (SC) in vivo. In recent years, it was shown that confocal Raman microspectroscopy can also be used for noninvasive in vivo depth-dependent determination of the physiological parameters of the SC, such as lamellar and lateral organization of intercellular lipids (ICLs), folding properties of keratin, water mobility, and hydrogen bonding states. The results showed that the strongest skin barrier function, which is primarily manifested by the orthorhombic organization of ICLs, is provided at ≈20-40% SC depth, which is related to the maximal bonding state of water with surrounding components in the SC. The secondary and tertiary structures of keratin determine water binding in the SC, which is depth-dependent. This paper shows the technical possibility and advantage of confocal Raman microspectroscopy in noninvasive investigation of the skin and summarizes recent results on in vivo investigation of the human SC.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":"35 3","pages":"125-136"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39680708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eduardo Anitua, Victoria Muñoz, Libe Aspe, Roberto Tierno, Adrian García-Salvador, Felipe Goñi-de-Cerio, Ander Pino
{"title":"In vitro and in vivo Effect of Platelet-Rich Plasma-Based Autologous Topical Serum on Cutaneous Wound Healing.","authors":"Eduardo Anitua, Victoria Muñoz, Libe Aspe, Roberto Tierno, Adrian García-Salvador, Felipe Goñi-de-Cerio, Ander Pino","doi":"10.1159/000517195","DOIUrl":"https://doi.org/10.1159/000517195","url":null,"abstract":"<p><strong>Introduction: </strong>Skin injury and wound healing is an inevitable event during lifetime. However, several complications may hamper the regeneration of the cutaneous tissue and lead to a chronic profile that prolongs patient recovery. Platelet-rich plasma is rising as an effective and safe alternative to the management of wounds. However, this technology presents some limitations such as the need for repeated blood extractions and health-care interventions.</p><p><strong>Objective: </strong>The aim of this study was to assess the use of an endogenous and storable topical serum (ES) derived from plasma rich in growth factors promoting wound healing, and to obtain preliminary data regarding its clinical and experimental effect over ulcerated skin models and patient care.</p><p><strong>Methods: </strong>Human dermal fibroblast and 3D organotypic ulcerated skin models were used to assess ES over the main mechanisms of wound healing including cell migration, edge contraction, collagen synthesis, tissue damage, extracellular matrix remodeling, cell death, metabolic activity, and histomorphometry analysis. Additionally, 4 patients suffering from skin wounds were treated and clinically assessed.</p><p><strong>Results: </strong>ES promoted dermal fibroblast migration, wound edge contraction, and collagen synthesis. When topically applied, ES increased collagen and elastin deposition and reduced tissue damage. The interstitial edema, structural integrity, and cell activity were also maintained, and apoptotic levels were reduced. Patients suffering from hard-to-heal wounds of different etiologies were treated with ES, and the ulcers healed completely within few weeks with no reported adverse events.</p><p><strong>Conclusion: </strong>This preliminary study suggests that ES might promote cutaneous wound healing and may be useful for accelerating the re-epithelization of skin ulcers.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":"35 1","pages":"51-64"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000517195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39172587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Markus Lubda, Maximilian Zander, Andrew Salazar, Harald Kolmar, Jörg von Hagen
{"title":"Lateral Dermal Penetration Is Dependent on the Lipophilicity of Active Ingredients.","authors":"Markus Lubda, Maximilian Zander, Andrew Salazar, Harald Kolmar, Jörg von Hagen","doi":"10.1159/000522633","DOIUrl":"https://doi.org/10.1159/000522633","url":null,"abstract":"<p><strong>Introduction: </strong>With its large surface area, skin facilitates a topical administration of active ingredients, and thus percutaneous delivery to a specific target site. Due to its high barrier function and different diffusion characteristics, skin governs the efficacy of these active ingredients and a bioavailability in the epidermal and dermal tissue.</p><p><strong>Objective: </strong>In order to characterize the vertical and lateral movement of molecules into and inside the skin, the diffusivity of active ingredients with different physicochemical properties and their penetration ability in different dermal skin layers was investigated.</p><p><strong>Methods: </strong>A novel lateral dermal microdialysis (MD) penetration setup was used to compare the diffusion characteristics of active ingredients into superficial and deep-implanted MD membranes in porcine skin. The corresponding membrane depth was determined via ultrasound and the active ingredients concentration via high-pressure liquid chromatography measurement.</p><p><strong>Results: </strong>The depth depended penetration of superficial and deep-implanted MD membranes and the quantitative diffusivity of two active ingredients was compared. An experimental lateral MD setup was used to determine the influence of percutaneous skin penetration characteristics of an active ingredient with different lipophilic and hydrophilic characteristics. Therefore, hydrophilic caffeine and lipophilic LIP1, which have an identical molecular weight but different lipophilic characteristics, were tested for their penetration ability inside a propylene glycol and oleic acid formulation.</p><p><strong>Conclusion: </strong>The vertical and lateral penetration movement of caffeine was found to exceed that of LIP1 through the hydrophilic dermal environment. The findings of this study show that the lipophilicity of active ingredients influences the penetration movement and that skin enables a conical increasing lateral diffusivity and transdermal delivery.</p>","PeriodicalId":21748,"journal":{"name":"Skin Pharmacology and Physiology","volume":"35 4","pages":"235-246"},"PeriodicalIF":2.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39929683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}