Abstract
CoQ10 is ubiquitously present in eukaryotic cells. It acts as electron carrier in the electron transport chain of the inner membrane of the mitochondria to facilitate aerobic cellular respiration. A highly stable lipid nanodispersion formulation containing CoQ10 (BPM31510) is currently in clinical investigation for treatment of cancer. This study was designed to determine whether biophysical interactions between CoQ10 and lipid, in part, explain the observed stability and cellular accumulation of CoQ10 in cells and tissues. A lipid monolayer at the air-water interface was used as an experimental membrane model to measure CoQ10 penetration and solubility. Lipid monolayers with varying proportions of CoQ10 were laterally compressed to measure CoQ10 miscibility and lateral organization. Additionally, lipid monolayers with varying lateral packing densities were spread at the air-water interface and CoQ10 was injected in proximity to measure its rate of penetration. Our results demonstrate that CoQ10 selectively penetrates into lipid monolayers with a lower lateral packing density, and is excluded by monolayers of higher packing densities. Data also indicates that CoQ10-lipid mixing is non-ideal. CoQ10 presence in lipid monolayers is biphasic, with one phase occupying the interstitial space between the DMPC lipids, and the other phase is present as pure CoQ10 domains. This work provides further insight into mechanism of action of CoQ10 based formulations that can significantly increase intracellular CoQ10 concentration to show pleotropic effects on cellular functions.
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