Photodegradation of Bexarotene and Its Implication for Cytotoxicity
A detailed understanding of the stability of an active pharmaceutical ingredient and a pharmaceutical dosage form is essential for the drug-development process and for safe and effective use of medicines. Photostability testing as an inherent part of stability studies provides valuable knowledge on...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/8/1220 |
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| author | Agata Kryczyk-Poprawa István Zupkó Péter Bérdi Paweł Żmudzki Joanna Piotrowska Elżbieta Pękala Aleksandra Berdys Bożena Muszyńska Włodzimierz Opoka |
| author_facet | Agata Kryczyk-Poprawa István Zupkó Péter Bérdi Paweł Żmudzki Joanna Piotrowska Elżbieta Pękala Aleksandra Berdys Bożena Muszyńska Włodzimierz Opoka |
| author_sort | Agata Kryczyk-Poprawa |
| collection | DOAJ |
| description | A detailed understanding of the stability of an active pharmaceutical ingredient and a pharmaceutical dosage form is essential for the drug-development process and for safe and effective use of medicines. Photostability testing as an inherent part of stability studies provides valuable knowledge on degradation pathways and structures of products generated under UV irradiation. Photostability is particularly important for topically administered drugs, as they are more exposed to UV radiation. Bexarotene is a more recent third-generation retinoid approved by the U.S. Food and Drug Administration and the European Medicines Agency as a topically applied anticancer agent. The present study aimed to assess bexarotene photostability, including the presence of UV filters, which have been permitted to be used in cosmetic products in Europe and the USA. The bexarotene photostability testing was performed in ethanol solutions and in formulations applied on PMMA plates. The UPLC-MS/MS technique was used to determine the tested substance. The presence of photocatalysts such as TiO<sub>2</sub> or ZnO, as well as the organic UV filters avobenzone, benzophenone-3, meradimate, and homosalate, could contribute to degradation of bexarotene under UV irradiation. Four photocatalytic degradation products of bexarotene were identified for the first time. The antiproliferative properties of the degradation products of bexarotene were assessed by MTT assay on a panel of human adherent cancer cells, and concentration-dependent growth inhibition was evidenced on all tested cell lines. The cytotoxicity of the formed products after 4 h of UV irradiation was significantly higher than that of the parent compound (<i>p</i> < 0.05). Furthermore non-cancerous murine fibroblasts exhibited marked concentration-dependent inhibition by bexarotene, while the degradation products elicited more pronounced antiproliferative action only at the highest applied concentration. |
| first_indexed | 2024-03-10T08:28:43Z |
| format | Article |
| id | doaj.art-d6432656c6f548f29954a97351418ad6 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T08:28:43Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d6432656c6f548f29954a97351418ad62023-11-22T09:14:31ZengMDPI AGPharmaceutics1999-49232021-08-01138122010.3390/pharmaceutics13081220Photodegradation of Bexarotene and Its Implication for CytotoxicityAgata Kryczyk-Poprawa0István Zupkó1Péter Bérdi2Paweł Żmudzki3Joanna Piotrowska4Elżbieta Pękala5Aleksandra Berdys6Bożena Muszyńska7Włodzimierz Opoka8Department of Inorganic and Analytical Chemistry, Jagiellonian University Medical College, 30-688 Kraków, PolandDepartment of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, HungaryDepartment of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, HungaryDepartment of Medicinal Chemistry, Jagiellonian University Medical College, 30-688 Kraków, PolandDepartment of Inorganic and Analytical Chemistry, Jagiellonian University Medical College, 30-688 Kraków, PolandDepartment of Pharmaceutical Biochemistry, Jagiellonian University Medical College, 30-688 Kraków, PolandIndependent Researchers, 30-688 Kraków, PolandDepartment of Pharmaceutical Botany, Jagiellonian University Collegium Medicum, 30-688 Kraków, PolandDepartment of Inorganic and Analytical Chemistry, Jagiellonian University Medical College, 30-688 Kraków, PolandA detailed understanding of the stability of an active pharmaceutical ingredient and a pharmaceutical dosage form is essential for the drug-development process and for safe and effective use of medicines. Photostability testing as an inherent part of stability studies provides valuable knowledge on degradation pathways and structures of products generated under UV irradiation. Photostability is particularly important for topically administered drugs, as they are more exposed to UV radiation. Bexarotene is a more recent third-generation retinoid approved by the U.S. Food and Drug Administration and the European Medicines Agency as a topically applied anticancer agent. The present study aimed to assess bexarotene photostability, including the presence of UV filters, which have been permitted to be used in cosmetic products in Europe and the USA. The bexarotene photostability testing was performed in ethanol solutions and in formulations applied on PMMA plates. The UPLC-MS/MS technique was used to determine the tested substance. The presence of photocatalysts such as TiO<sub>2</sub> or ZnO, as well as the organic UV filters avobenzone, benzophenone-3, meradimate, and homosalate, could contribute to degradation of bexarotene under UV irradiation. Four photocatalytic degradation products of bexarotene were identified for the first time. The antiproliferative properties of the degradation products of bexarotene were assessed by MTT assay on a panel of human adherent cancer cells, and concentration-dependent growth inhibition was evidenced on all tested cell lines. The cytotoxicity of the formed products after 4 h of UV irradiation was significantly higher than that of the parent compound (<i>p</i> < 0.05). Furthermore non-cancerous murine fibroblasts exhibited marked concentration-dependent inhibition by bexarotene, while the degradation products elicited more pronounced antiproliferative action only at the highest applied concentration.https://www.mdpi.com/1999-4923/13/8/1220bexarotenephotostabilityUV absorbersthird-generation retinoids |
| spellingShingle | Agata Kryczyk-Poprawa István Zupkó Péter Bérdi Paweł Żmudzki Joanna Piotrowska Elżbieta Pękala Aleksandra Berdys Bożena Muszyńska Włodzimierz Opoka Photodegradation of Bexarotene and Its Implication for Cytotoxicity Pharmaceutics bexarotene photostability UV absorbers third-generation retinoids |
| title | Photodegradation of Bexarotene and Its Implication for Cytotoxicity |
| title_full | Photodegradation of Bexarotene and Its Implication for Cytotoxicity |
| title_fullStr | Photodegradation of Bexarotene and Its Implication for Cytotoxicity |
| title_full_unstemmed | Photodegradation of Bexarotene and Its Implication for Cytotoxicity |
| title_short | Photodegradation of Bexarotene and Its Implication for Cytotoxicity |
| title_sort | photodegradation of bexarotene and its implication for cytotoxicity |
| topic | bexarotene photostability UV absorbers third-generation retinoids |
| url | https://www.mdpi.com/1999-4923/13/8/1220 |
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