Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels
Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrol...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/8/394 |
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| author | Fiorenza Rancan Hildburg Volkmann Michael Giulbudagian Fabian Schumacher Jessica Isolde Stanko Burkhard Kleuser Ulrike Blume-Peytavi Marcelo Calderón Annika Vogt |
| author_facet | Fiorenza Rancan Hildburg Volkmann Michael Giulbudagian Fabian Schumacher Jessica Isolde Stanko Burkhard Kleuser Ulrike Blume-Peytavi Marcelo Calderón Annika Vogt |
| author_sort | Fiorenza Rancan |
| collection | DOAJ |
| description | Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions. |
| first_indexed | 2024-04-13T06:47:38Z |
| format | Article |
| id | doaj.art-6cd81cd102ee424eb77534c8af9bfe66 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-13T06:47:38Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6cd81cd102ee424eb77534c8af9bfe662022-12-22T02:57:32ZengMDPI AGPharmaceutics1999-49232019-08-0111839410.3390/pharmaceutics11080394pharmaceutics11080394Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based NanogelsFiorenza Rancan0Hildburg Volkmann1Michael Giulbudagian2Fabian Schumacher3Jessica Isolde Stanko4Burkhard Kleuser5Ulrike Blume-Peytavi6Marcelo Calderón7Annika Vogt8Clinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, GermanyClinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, GermanyInstitute of Nutritional Science, Department of Nutritional Toxicology, University of Potsdam, 14558 Nuthetal, GermanyClinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, GermanyInstitute of Nutritional Science, Department of Nutritional Toxicology, University of Potsdam, 14558 Nuthetal, GermanyClinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, GermanyInstitut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, GermanyClinical Research Center for Hair and Skin Science, Department of Dermatology and Allergy, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, GermanyPolyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions.https://www.mdpi.com/1999-4923/11/8/394tacrolimus formulationnanogelsskin penetrationdrug deliveryhuman excised skinJurkat cells |
| spellingShingle | Fiorenza Rancan Hildburg Volkmann Michael Giulbudagian Fabian Schumacher Jessica Isolde Stanko Burkhard Kleuser Ulrike Blume-Peytavi Marcelo Calderón Annika Vogt Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels Pharmaceutics tacrolimus formulation nanogels skin penetration drug delivery human excised skin Jurkat cells |
| title | Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels |
| title_full | Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels |
| title_fullStr | Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels |
| title_full_unstemmed | Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels |
| title_short | Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels |
| title_sort | dermal delivery of the high molecular weight drug tacrolimus by means of polyglycerol based nanogels |
| topic | tacrolimus formulation nanogels skin penetration drug delivery human excised skin Jurkat cells |
| url | https://www.mdpi.com/1999-4923/11/8/394 |
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