Micellization of coenzyme Q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrations
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".