Micellization of coenzyme Q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrations
Coenzyme Q10 (CoQ10; also known as ubiquinone) is a vital, redox-active membrane component that functions as obligate electron transporter in the mitochondrial respiratory chain, as cofactor in other enzymatic processes and as antioxidant. CoQ10 supplementation has been widely investigated for treat...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231720308855 |
| _version_ | 1818159844465573888 |
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| author | Ying Wang Siegfried Hekimi |
| author_facet | Ying Wang Siegfried Hekimi |
| author_sort | Ying Wang |
| collection | DOAJ |
| description | Coenzyme Q10 (CoQ10; also known as ubiquinone) is a vital, redox-active membrane component that functions as obligate electron transporter in the mitochondrial respiratory chain, as cofactor in other enzymatic processes and as antioxidant. CoQ10 supplementation has been widely investigated for treating a variety of acute and chronic conditions in which mitochondrial function or oxidative stress play a role. In addition, it is used as replacement therapy in patients with CoQ deficiency including inborn primary CoQ10 deficiency due to mutations in CoQ10-biosynthetic genes as well as secondary CoQ10 deficiency, which is frequently observed in patients with mitochondrial disease syndrome and in other conditions. However, despite many tests and some promising results, whether CoQ10 treatment is beneficial in any indication has remained inconclusive. Because CoQ10 is highly insoluble, it is only available in oral formulations, despite its very poor oral bioavailability. Using a novel model of CoQ-deficient cells, we screened a library of FDA-approved drugs for an activity that could increase the uptake of exogenous CoQ10 by the cell. We identified the fungicide caspofungin as capable of increasing the aqueous solubility of CoQ10 by several orders of magnitude. Caspofungin is a mild surfactant that solubilizes CoQ10 by forming nano-micelles with unique properties favoring stability and cellular uptake. Intravenous administration of the formulation in mice achieves unprecedented increases in CoQ10 plasma levels and in tissue uptake, with no observable toxicity. As it contains only two safe components (caspofungin and CoQ10), this injectable formulation presents a high potential for clinical safety and efficacy. |
| first_indexed | 2024-12-11T15:52:26Z |
| format | Article |
| id | doaj.art-92fa4f4ce10a493c85190e1a247387d5 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-11T15:52:26Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-92fa4f4ce10a493c85190e1a247387d52022-12-22T00:59:32ZengElsevierRedox Biology2213-23172020-09-0136101680Micellization of coenzyme Q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrationsYing Wang0Siegfried Hekimi1Department of Biology, McGill University, Montreal, Quebec, CanadaCorresponding author.; Department of Biology, McGill University, Montreal, Quebec, CanadaCoenzyme Q10 (CoQ10; also known as ubiquinone) is a vital, redox-active membrane component that functions as obligate electron transporter in the mitochondrial respiratory chain, as cofactor in other enzymatic processes and as antioxidant. CoQ10 supplementation has been widely investigated for treating a variety of acute and chronic conditions in which mitochondrial function or oxidative stress play a role. In addition, it is used as replacement therapy in patients with CoQ deficiency including inborn primary CoQ10 deficiency due to mutations in CoQ10-biosynthetic genes as well as secondary CoQ10 deficiency, which is frequently observed in patients with mitochondrial disease syndrome and in other conditions. However, despite many tests and some promising results, whether CoQ10 treatment is beneficial in any indication has remained inconclusive. Because CoQ10 is highly insoluble, it is only available in oral formulations, despite its very poor oral bioavailability. Using a novel model of CoQ-deficient cells, we screened a library of FDA-approved drugs for an activity that could increase the uptake of exogenous CoQ10 by the cell. We identified the fungicide caspofungin as capable of increasing the aqueous solubility of CoQ10 by several orders of magnitude. Caspofungin is a mild surfactant that solubilizes CoQ10 by forming nano-micelles with unique properties favoring stability and cellular uptake. Intravenous administration of the formulation in mice achieves unprecedented increases in CoQ10 plasma levels and in tissue uptake, with no observable toxicity. As it contains only two safe components (caspofungin and CoQ10), this injectable formulation presents a high potential for clinical safety and efficacy.http://www.sciencedirect.com/science/article/pii/S2213231720308855Coenzyme QUbiquinoneMitochondrial diseasesMicelleCaspofungin |
| spellingShingle | Ying Wang Siegfried Hekimi Micellization of coenzyme Q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrations Redox Biology Coenzyme Q Ubiquinone Mitochondrial diseases Micelle Caspofungin |
| title | Micellization of coenzyme Q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrations |
| title_full | Micellization of coenzyme Q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrations |
| title_fullStr | Micellization of coenzyme Q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrations |
| title_full_unstemmed | Micellization of coenzyme Q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrations |
| title_short | Micellization of coenzyme Q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrations |
| title_sort | micellization of coenzyme q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrations |
| topic | Coenzyme Q Ubiquinone Mitochondrial diseases Micelle Caspofungin |
| url | http://www.sciencedirect.com/science/article/pii/S2213231720308855 |
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