Coenzyme Q10 Loaded DQAsomes for Leigh Disease

Abstract Leigh syndrome (LS), a rare hereditary neurometabolic disorder caused by mitochondrial dysfunction, results from genetic mutations affecting the central nervous system. Endogenous bioactive antioxidant Coenzyme Q10 (CoQ10) deficiency is associated with LS and contributes to various clinical symptoms. Dequalinium chloride (DQA) is a bolalipid with mitochondria-targeting properties. This study aimed to develop CoQ10-loaded DQAsomes to enhance CoQ10 solubility and delivery to mitochondria for potential LS treatment. Human pluripotent cell lines (HPP) and MDCi007-A cells with NDUFV gene anomalies were utilized. DQAsomes were prepared using thin-film technique and characterized for size, zeta potential, encapsulation efficiency, and process efficiency. Drug release, dissolution, and cytotoxicity studies were performed. RT-PCR, ELISA, immunostaining, and Western blot analyses assessed pluripotency and gene expression changes and apoptosis induced by the formulations. DQAsomes exhibited sizes between 165.8-311.2 nm, with anionic zeta potential. Encapsulation efficiency ranged from 34.03–82.48%. Cytotoxicity studies demonstrated improved viability with CoQ10-DQA compared to CoQ10-PBS. CoQ10-DQAsignificantly reduced the expression of pluripotency markers OCT3/4, SOX-2, and NANOG, potentially indicating reduced stemness. CoQ10-loaded DQAsomes present a promising strategy for addressing CoQ10 deficiency in LS. These DQAsomes enhance CoQ10 solubility and bioavailability while potentially modulating cellular pluripotency markers and mitochondrial gene expression.