Topical Drug Delivery of Concentrated Cabazitaxel in an α‐Tocopherol and DMSO Solution
Abstract Topical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad‐spectrum second‐generation taxane cytotoxic agent, can be dissolved in α‐tocopherol at high concentrations exceeding 100 mg mL−1. 2D nuclear magnetic resonanc...
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| Format: | Article |
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Wiley
2023-10-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202302658 |
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| author | Boyang Sun Georgios Paraskevopoulos Jiwei Min Robert Rossdeutcher Sanjana Ghosh Breandan Quinn Meng‐Hsuan Lin Debanjan Sarkar Dinesh Sukumaran Yuefei Wang Kateřina Vávrová Jonathan F. Lovell Yumiao Zhang |
| author_facet | Boyang Sun Georgios Paraskevopoulos Jiwei Min Robert Rossdeutcher Sanjana Ghosh Breandan Quinn Meng‐Hsuan Lin Debanjan Sarkar Dinesh Sukumaran Yuefei Wang Kateřina Vávrová Jonathan F. Lovell Yumiao Zhang |
| author_sort | Boyang Sun |
| collection | DOAJ |
| description | Abstract Topical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad‐spectrum second‐generation taxane cytotoxic agent, can be dissolved in α‐tocopherol at high concentrations exceeding 100 mg mL−1. 2D nuclear magnetic resonance (NMR) analysis and molecular dynamics (MD) are used to study this phenomenon. The addition of 30% dimethyl sulfoxide (DMSO) to the α‐tocopherol/CTX solution improves its working viscosity and enhances CTX permeation through human skin in vitro (over 5 µg cm−2 within 24 h), while no detectable drug permeates when CTX is dissolved in α‐tocopherol alone. In a transepidermal water loss assay, the barrier impairment induced by CTX in 30% DMSO in α‐tocopherol, but not in pure DMSO, is reversible 8 h after the formulation removal from the skin surface. Antitumor efficacy of the topical CTX formulation is evaluated in nude mice bearing A431 human squamous carcinoma skin cancer xenografts. With topical application of concentrated CTX solutions (75 mg mL−1), tumor growth is significantly suppressed compared to lower concentration groups (0, 25, or 50 mg mL−1 CTX). Taken together, these findings show that topical delivery of CTX using a DMSO and α‐tocopherol solvent warrants further study as a treatment for skin malignancies. |
| format | Article |
| id | doaj-art-a82d9f63c0f8496e8d4524c280b3ca62 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-a82d9f63c0f8496e8d4524c280b3ca622024-11-22T13:11:49ZengWileyAdvanced Science2198-38442023-10-011029n/an/a10.1002/advs.202302658Topical Drug Delivery of Concentrated Cabazitaxel in an α‐Tocopherol and DMSO SolutionBoyang Sun0Georgios Paraskevopoulos1Jiwei Min2Robert Rossdeutcher3Sanjana Ghosh4Breandan Quinn5Meng‐Hsuan Lin6Debanjan Sarkar7Dinesh Sukumaran8Yuefei Wang9Kateřina Vávrová10Jonathan F. Lovell11Yumiao Zhang12School of Chemical Engineering and Technology Key Laboratory of Systems Bioengineering (Ministry of Education) Frontiers Science Center for Synthetic Biology (Ministry of Education) State Key Laboratory of Chemical Engineering Tianjin University Tianjin 300350 P. R. ChinaSkin Barrier Research Group Faculty of Pharmacy Charles University Akademika Heyrovského 1203 Hradec Králové 50005 Czech RepublicSchool of Chemical Engineering and Technology Key Laboratory of Systems Bioengineering (Ministry of Education) Frontiers Science Center for Synthetic Biology (Ministry of Education) State Key Laboratory of Chemical Engineering Tianjin University Tianjin 300350 P. R. ChinaDepartment of Chemistry State University of New York at Buffalo Buffalo NY 14260 USADepartment of Biomedical Engineering State University of New York at Buffalo Buffalo NY 14260 USADepartment of Biomedical Engineering State University of New York at Buffalo Buffalo NY 14260 USADepartment of Biomedical Engineering State University of New York at Buffalo Buffalo NY 14260 USADepartment of Biomedical Engineering State University of New York at Buffalo Buffalo NY 14260 USADepartment of Chemistry State University of New York at Buffalo Buffalo NY 14260 USASchool of Chemical Engineering and Technology Key Laboratory of Systems Bioengineering (Ministry of Education) Frontiers Science Center for Synthetic Biology (Ministry of Education) State Key Laboratory of Chemical Engineering Tianjin University Tianjin 300350 P. R. ChinaSkin Barrier Research Group Faculty of Pharmacy Charles University Akademika Heyrovského 1203 Hradec Králové 50005 Czech RepublicDepartment of Biomedical Engineering State University of New York at Buffalo Buffalo NY 14260 USASchool of Chemical Engineering and Technology Key Laboratory of Systems Bioengineering (Ministry of Education) Frontiers Science Center for Synthetic Biology (Ministry of Education) State Key Laboratory of Chemical Engineering Tianjin University Tianjin 300350 P. R. ChinaAbstract Topical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad‐spectrum second‐generation taxane cytotoxic agent, can be dissolved in α‐tocopherol at high concentrations exceeding 100 mg mL−1. 2D nuclear magnetic resonance (NMR) analysis and molecular dynamics (MD) are used to study this phenomenon. The addition of 30% dimethyl sulfoxide (DMSO) to the α‐tocopherol/CTX solution improves its working viscosity and enhances CTX permeation through human skin in vitro (over 5 µg cm−2 within 24 h), while no detectable drug permeates when CTX is dissolved in α‐tocopherol alone. In a transepidermal water loss assay, the barrier impairment induced by CTX in 30% DMSO in α‐tocopherol, but not in pure DMSO, is reversible 8 h after the formulation removal from the skin surface. Antitumor efficacy of the topical CTX formulation is evaluated in nude mice bearing A431 human squamous carcinoma skin cancer xenografts. With topical application of concentrated CTX solutions (75 mg mL−1), tumor growth is significantly suppressed compared to lower concentration groups (0, 25, or 50 mg mL−1 CTX). Taken together, these findings show that topical delivery of CTX using a DMSO and α‐tocopherol solvent warrants further study as a treatment for skin malignancies.https://doi.org/10.1002/advs.202302658cabazitaxelskin cancertransdermal deliveryα‐tocopherol |
| spellingShingle | Boyang Sun Georgios Paraskevopoulos Jiwei Min Robert Rossdeutcher Sanjana Ghosh Breandan Quinn Meng‐Hsuan Lin Debanjan Sarkar Dinesh Sukumaran Yuefei Wang Kateřina Vávrová Jonathan F. Lovell Yumiao Zhang Topical Drug Delivery of Concentrated Cabazitaxel in an α‐Tocopherol and DMSO Solution Advanced Science cabazitaxel skin cancer transdermal delivery α‐tocopherol |
| title | Topical Drug Delivery of Concentrated Cabazitaxel in an α‐Tocopherol and DMSO Solution |
| title_full | Topical Drug Delivery of Concentrated Cabazitaxel in an α‐Tocopherol and DMSO Solution |
| title_fullStr | Topical Drug Delivery of Concentrated Cabazitaxel in an α‐Tocopherol and DMSO Solution |
| title_full_unstemmed | Topical Drug Delivery of Concentrated Cabazitaxel in an α‐Tocopherol and DMSO Solution |
| title_short | Topical Drug Delivery of Concentrated Cabazitaxel in an α‐Tocopherol and DMSO Solution |
| title_sort | topical drug delivery of concentrated cabazitaxel in an α tocopherol and dmso solution |
| topic | cabazitaxel skin cancer transdermal delivery α‐tocopherol |
| url | https://doi.org/10.1002/advs.202302658 |
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