Coenzyme Q10 (CoQ10) is a lipid-soluble redox cofactor essential for mitochondrial electron transport, membrane stabilization, and antioxidant defense in its reduced form. Broad clinical utility has been hampered by poor oral bioavailability and low tissue uptake using nutraceutical formulations. BPM31510 is a novel pharmaceutical nanotechnology formulated with oxidized CoQ10 as a lipid nanoparticle designed to enhance systemic exposure and mitochondrial concentration. Using UHPLC-MS/MS, we quantified oxidized CoQ10, reduced CoQ10, and oxidized CoQ9 in BPM31510- and CoQ10-treated SH-SY5Y neuroblastoma cells following para-aminobenzoic acid (PABA)-induced CoQ deficiency. BPM31510 significantly increased all three analytes and raised ATP content in SH-SY5Y cells more effectively than solubilized CoQ10. In patient-derived fibroblasts with PDSS2, COQ2, or COQ8A mutations, BPM31510 outperformed nutraceutical formulations in enriching CoQ10 levels. In vivo, C57BL/6J mice received BPM31510 (10 or 50 mg/kg, intraperitoneal) or oral CoQ10 twice daily for 14 days. BPM31510 substantially increased oxidized and reduced CoQ10 in plasma, liver, heart, and adipose tissue, enhancing the overall CoQ pool relative to oral CoQ10. MALDI mass spectrometry imaging confirmed oxidized CoQ10 accumulation in myocardial tissue beyond the vasculature, consistent with UHPLC-MS/MS findings. These results demonstrate that BPM31510 targets bioactive CoQ10 to metabolically active tissues, overcoming limitations of oral supplementation, and may provide therapeutic benefit for primary and secondary CoQ10 deficiencies and other mitochondrial or metabolic disorders marked by impaired redox balance and energy homeostasis.
Aristizabal‐Henao et al. (Fri,) studied this question.