Micellization of coenzyme Q by the fungicide caspofungin allows for safe intravenous administration to reach extreme supraphysiological concentrations

Coenzyme Q(10) (CoQ(10); 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. CoQ(10) 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 CoQ(10) deficiency due to mutations in CoQ(10)-biosynthetic genes as well as secondary CoQ(10) deficiency, which is frequently observed in patients with mitochondrial disease syndrome and in other conditions. However, despite many tests and some promising results, whether CoQ(10) treatment is beneficial in any indication has remained inconclusive. Because CoQ(10) 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 CoQ(10) by the cell. We identified the fungicide caspofungin as capable of increasing the aqueous solubility of CoQ(10) by several orders of magnitude. Caspofungin is a mild surfactant that solubilizes CoQ(10) by forming nano-micelles with unique properties favoring stability and cellular uptake. Intravenous administration of the formulation in mice achieves unprecedented increases in CoQ(10) plasma levels and in tissue uptake, with no observable toxicity. As it contains only two safe components (caspofungin and CoQ(10)), this injectable formulation presents a high potential for clinical safety and efficacy.