Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases
Tofacitinib (TFB), a Janus kinase inhibitor, has shown excellent success off-label in treating various dermatological diseases, especially alopecia areata (AA). However, TFB’s safe and targeted delivery into hair follicles (HFs) is highly desirable due to its systemic adverse effects. Nanoparticles...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/12/1131 |
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| author | Rebekka Christmann Duy-Khiet Ho Jenny Wilzopolski Sangeun Lee Marcus Koch Brigitta Loretz Thomas Vogt Wolfgang Bäumer Ulrich F. Schaefer Claus-Michael Lehr |
| author_facet | Rebekka Christmann Duy-Khiet Ho Jenny Wilzopolski Sangeun Lee Marcus Koch Brigitta Loretz Thomas Vogt Wolfgang Bäumer Ulrich F. Schaefer Claus-Michael Lehr |
| author_sort | Rebekka Christmann |
| collection | DOAJ |
| description | Tofacitinib (TFB), a Janus kinase inhibitor, has shown excellent success off-label in treating various dermatological diseases, especially alopecia areata (AA). However, TFB’s safe and targeted delivery into hair follicles (HFs) is highly desirable due to its systemic adverse effects. Nanoparticles (NPs) can enhance targeted follicular drug delivery and minimize interfollicular permeation and thereby reduce systemic drug exposure. In this study, we report a facile method to assemble the stable and uniform 240 nm TFB loaded squalenyl derivative (SqD) nanoparticles (TFB SqD NPs) in aqueous solution, which allowed an excellent loading capacity (LC) of 20%. The SqD NPs showed an enhanced TFB delivery into HFs compared to the aqueous formulations of plain drug in an <i>ex vivo</i> pig ear model. Furthermore, the therapeutic efficacy of the TFB SqD NPs was studied in a mouse model of allergic dermatitis by ear swelling reduction and compared to TFB dissolved in a non-aqueous mixture of acetone and DMSO (7:1 <i>v</i>/<i>v</i>). Whereas such formulation would not be acceptable for use in the clinic, the TFB SqD NPs dispersed in water illustrated a better reduction in inflammatory effects than plain TFB’s aqueous formulation, implying both encouraging good <i>in vivo</i> efficacy and safety. These findings support the potential of TFB SqD NPs for developing a long-term topical therapy of AA. |
| first_indexed | 2024-03-10T14:37:19Z |
| format | Article |
| id | doaj.art-d4a9aebe5346444a96214083fbc832a6 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T14:37:19Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d4a9aebe5346444a96214083fbc832a62023-11-20T22:05:11ZengMDPI AGPharmaceutics1999-49232020-11-011212113110.3390/pharmaceutics12121131Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin DiseasesRebekka Christmann0Duy-Khiet Ho1Jenny Wilzopolski2Sangeun Lee3Marcus Koch4Brigitta Loretz5Thomas Vogt6Wolfgang Bäumer7Ulrich F. Schaefer8Claus-Michael Lehr9Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS)—Helmholtz Centre for Infection Research (HZI), 66123 Saarbrücken, GermanyHelmholtz-Institute for Pharmaceutical Research Saarland (HIPS)—Helmholtz Centre for Infection Research (HZI), 66123 Saarbrücken, GermanyInstitute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universität Berlin, 14195 Berlin, GermanyHelmholtz-Institute for Pharmaceutical Research Saarland (HIPS)—Helmholtz Centre for Infection Research (HZI), 66123 Saarbrücken, GermanyINM-Leibniz Institute for New Materials, 66123 Saarbrücken, GermanyHelmholtz-Institute for Pharmaceutical Research Saarland (HIPS)—Helmholtz Centre for Infection Research (HZI), 66123 Saarbrücken, GermanyDepartment of Dermatology, Saarland University Hospital, 66421 Homburg/Saar, GermanyInstitute of Pharmacology and Toxicology, Department of Veterinary Medicine, Freie Universität Berlin, 14195 Berlin, GermanyDepartment of Pharmacy, Saarland University, 66123 Saarbrücken, GermanyHelmholtz-Institute for Pharmaceutical Research Saarland (HIPS)—Helmholtz Centre for Infection Research (HZI), 66123 Saarbrücken, GermanyTofacitinib (TFB), a Janus kinase inhibitor, has shown excellent success off-label in treating various dermatological diseases, especially alopecia areata (AA). However, TFB’s safe and targeted delivery into hair follicles (HFs) is highly desirable due to its systemic adverse effects. Nanoparticles (NPs) can enhance targeted follicular drug delivery and minimize interfollicular permeation and thereby reduce systemic drug exposure. In this study, we report a facile method to assemble the stable and uniform 240 nm TFB loaded squalenyl derivative (SqD) nanoparticles (TFB SqD NPs) in aqueous solution, which allowed an excellent loading capacity (LC) of 20%. The SqD NPs showed an enhanced TFB delivery into HFs compared to the aqueous formulations of plain drug in an <i>ex vivo</i> pig ear model. Furthermore, the therapeutic efficacy of the TFB SqD NPs was studied in a mouse model of allergic dermatitis by ear swelling reduction and compared to TFB dissolved in a non-aqueous mixture of acetone and DMSO (7:1 <i>v</i>/<i>v</i>). Whereas such formulation would not be acceptable for use in the clinic, the TFB SqD NPs dispersed in water illustrated a better reduction in inflammatory effects than plain TFB’s aqueous formulation, implying both encouraging good <i>in vivo</i> efficacy and safety. These findings support the potential of TFB SqD NPs for developing a long-term topical therapy of AA.https://www.mdpi.com/1999-4923/12/12/1131targeted drug deliveryhair follicle<i>in vivo</i> allergic dermatitis mouse modelfollicular deliveryinterfollicular deliverynanoparticles |
| spellingShingle | Rebekka Christmann Duy-Khiet Ho Jenny Wilzopolski Sangeun Lee Marcus Koch Brigitta Loretz Thomas Vogt Wolfgang Bäumer Ulrich F. Schaefer Claus-Michael Lehr Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases Pharmaceutics targeted drug delivery hair follicle <i>in vivo</i> allergic dermatitis mouse model follicular delivery interfollicular delivery nanoparticles |
| title | Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases |
| title_full | Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases |
| title_fullStr | Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases |
| title_full_unstemmed | Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases |
| title_short | Tofacitinib Loaded Squalenyl Nanoparticles for Targeted Follicular Delivery in Inflammatory Skin Diseases |
| title_sort | tofacitinib loaded squalenyl nanoparticles for targeted follicular delivery in inflammatory skin diseases |
| topic | targeted drug delivery hair follicle <i>in vivo</i> allergic dermatitis mouse model follicular delivery interfollicular delivery nanoparticles |
| url | https://www.mdpi.com/1999-4923/12/12/1131 |
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