Cationic Vitamin E-TPGS Mixed Micelles of Berberine to Neutralize Doxorubicin-Induced Cardiotoxicity via Amelioration of Mitochondrial Dysfunction and Impeding Apoptosis
Anthracycline antibiotics, namely, doxorubicin (DOX) and daunorubicin, are among the most widely used anticancer therapies, yet are notoriously associated with severe myocardial damage due to oxidative stress and mitochondrial damage. Studies have indicated the strong pharmacological properties of B...
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MDPI AG
2024-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/5/1155 |
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| author | Abdelkader A. Metwally Samayita Ganguly Nora Biomi Mingyi Yao Tamer Elbayoumi |
| author_facet | Abdelkader A. Metwally Samayita Ganguly Nora Biomi Mingyi Yao Tamer Elbayoumi |
| author_sort | Abdelkader A. Metwally |
| collection | DOAJ |
| description | Anthracycline antibiotics, namely, doxorubicin (DOX) and daunorubicin, are among the most widely used anticancer therapies, yet are notoriously associated with severe myocardial damage due to oxidative stress and mitochondrial damage. Studies have indicated the strong pharmacological properties of Berberine (Brb) alkaloid, predominantly mediated via mitochondrial functions and nuclear networks. Despite the recent emphasis on Brb in clinical cardioprotective studies, pharmaceutical limitations hamper its clinical use. A nanoformulation for Brb was developed (mMic), incorporating a cationic lipid, oleylamine (OA), into the TPGS-mixed corona of PEGylated-phosphatidylethanolamine (PEG-PE) micelles. Cationic TPGS/PEG-PE mMic with superior Brb loading and stability markedly enhanced both intracellular and mitochondria-tropic Brb activities in cardiovascular muscle cells. Sub-lethal doses of Brb via cationic OA/TPGS mMic, as a DOX co-treatment, resulted in significant mitochondrial apoptosis suppression. In combination with an intense DOX challenge (up to ~50 µM), mitochondria-protective Brb-OA/TPGS mMic showed a significant 24 h recovery of cell viability (<i>p</i> ≤ 0.05–0.01). Mechanistically, the significant relative reduction in apoptotic caspase-9 and elevation of antiapoptotic Bcl-2 seem to mediate the cardioprotective role of Brb-OA/TPGS mMic against DOX. Our report aims to demonstrate the great potential of cationic OA/TPGS-mMic to selectively enhance the protective mitohormetic effect of Brb to mitigate DOX cardiotoxicity. |
| first_indexed | 2024-04-25T00:23:21Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-25T00:23:21Z |
| publishDate | 2024-03-01 |
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| series | Molecules |
| spelling | doaj.art-71393793b6974387b3fa3f6874f4fd402024-03-12T16:51:18ZengMDPI AGMolecules1420-30492024-03-01295115510.3390/molecules29051155Cationic Vitamin E-TPGS Mixed Micelles of Berberine to Neutralize Doxorubicin-Induced Cardiotoxicity via Amelioration of Mitochondrial Dysfunction and Impeding ApoptosisAbdelkader A. Metwally0Samayita Ganguly1Nora Biomi2Mingyi Yao3Tamer Elbayoumi4Department of Pharmaceutics, College of Pharmacy, Health Science Center (HSC), Kuwait University, P.O. Box 24923, Safat 13110, KuwaitParkinson’s Disease Research Unit, Department of Neurobiology, Barrow Neurological Institute, Dignity Health/St. Joseph’s Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ 85013, USAPharmacology and Toxicology Program, New College of Interdisciplinary Arts and Sciences, West Valley Campus, Arizona State University, N. 47th Ave & University Way, Glendale, AZ 85306, USADepartment of Pharmaceutical Sciences, Glendale Campus (CPG), College of Pharmacy, Midwestern University, 218-Cholla Hall, 19555 N. 59th Ave., Glendale, AZ 85308, USADepartment of Pharmaceutical Sciences, Glendale Campus (CPG), College of Pharmacy, Midwestern University, 218-Cholla Hall, 19555 N. 59th Ave., Glendale, AZ 85308, USAAnthracycline antibiotics, namely, doxorubicin (DOX) and daunorubicin, are among the most widely used anticancer therapies, yet are notoriously associated with severe myocardial damage due to oxidative stress and mitochondrial damage. Studies have indicated the strong pharmacological properties of Berberine (Brb) alkaloid, predominantly mediated via mitochondrial functions and nuclear networks. Despite the recent emphasis on Brb in clinical cardioprotective studies, pharmaceutical limitations hamper its clinical use. A nanoformulation for Brb was developed (mMic), incorporating a cationic lipid, oleylamine (OA), into the TPGS-mixed corona of PEGylated-phosphatidylethanolamine (PEG-PE) micelles. Cationic TPGS/PEG-PE mMic with superior Brb loading and stability markedly enhanced both intracellular and mitochondria-tropic Brb activities in cardiovascular muscle cells. Sub-lethal doses of Brb via cationic OA/TPGS mMic, as a DOX co-treatment, resulted in significant mitochondrial apoptosis suppression. In combination with an intense DOX challenge (up to ~50 µM), mitochondria-protective Brb-OA/TPGS mMic showed a significant 24 h recovery of cell viability (<i>p</i> ≤ 0.05–0.01). Mechanistically, the significant relative reduction in apoptotic caspase-9 and elevation of antiapoptotic Bcl-2 seem to mediate the cardioprotective role of Brb-OA/TPGS mMic against DOX. Our report aims to demonstrate the great potential of cationic OA/TPGS-mMic to selectively enhance the protective mitohormetic effect of Brb to mitigate DOX cardiotoxicity.https://www.mdpi.com/1420-3049/29/5/1155anthracycline antibioticsdoxorubicincardiomyopathyapoptosisberberinemitohormetic |
| spellingShingle | Abdelkader A. Metwally Samayita Ganguly Nora Biomi Mingyi Yao Tamer Elbayoumi Cationic Vitamin E-TPGS Mixed Micelles of Berberine to Neutralize Doxorubicin-Induced Cardiotoxicity via Amelioration of Mitochondrial Dysfunction and Impeding Apoptosis Molecules anthracycline antibiotics doxorubicin cardiomyopathy apoptosis berberine mitohormetic |
| title | Cationic Vitamin E-TPGS Mixed Micelles of Berberine to Neutralize Doxorubicin-Induced Cardiotoxicity via Amelioration of Mitochondrial Dysfunction and Impeding Apoptosis |
| title_full | Cationic Vitamin E-TPGS Mixed Micelles of Berberine to Neutralize Doxorubicin-Induced Cardiotoxicity via Amelioration of Mitochondrial Dysfunction and Impeding Apoptosis |
| title_fullStr | Cationic Vitamin E-TPGS Mixed Micelles of Berberine to Neutralize Doxorubicin-Induced Cardiotoxicity via Amelioration of Mitochondrial Dysfunction and Impeding Apoptosis |
| title_full_unstemmed | Cationic Vitamin E-TPGS Mixed Micelles of Berberine to Neutralize Doxorubicin-Induced Cardiotoxicity via Amelioration of Mitochondrial Dysfunction and Impeding Apoptosis |
| title_short | Cationic Vitamin E-TPGS Mixed Micelles of Berberine to Neutralize Doxorubicin-Induced Cardiotoxicity via Amelioration of Mitochondrial Dysfunction and Impeding Apoptosis |
| title_sort | cationic vitamin e tpgs mixed micelles of berberine to neutralize doxorubicin induced cardiotoxicity via amelioration of mitochondrial dysfunction and impeding apoptosis |
| topic | anthracycline antibiotics doxorubicin cardiomyopathy apoptosis berberine mitohormetic |
| url | https://www.mdpi.com/1420-3049/29/5/1155 |
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