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    Assessing the performance of Coenzyme Q10 loaded DQAsomes to treat Leigh syndrome caused by NDUFS4 knockout
    (Editions de Sante, 2024) Uner B.; Ergin A.D.; Celik A.; Khatik R.; Dwivedi P.
    Homozygous mutations in the NDUFS4 gene result in one of the many autosomal recessive forms of Leigh syndrome (LS), which impairs mitochondrial complex I function. In time, this disorder results in mental and motor impairment, often resulting in death. LS has no cure, and treatment focuses on symptom management. The delivery of CoQ10 can be improved in treating LS when caused by mutations in the NDUFS4 gene. Its poor solubility and bioavailability limit its clinical use as a preventative for oxidative damage and mitochondrial function. In this study, we developed CoQ10-loaded DQAsomes, utilizing dequalinium chloride -a bolalipid known for its antimicrobial properties to improve mitochondrial delivery of CoQ10. These DQAsomes were evaluated in an NDUFS4 knockout mouse model. Mitochondria from lung tissue of 32 knock-out mice and matched controls were isolated and CoQ10 uptake was quantified using fluorescence microscopy. Mitochondrial proteins were measured through ELISA, Western Blot, and PCR, and histopathological examination was performed to support the findings. The DQAsomes were measured to be approximately 151.3 nm with a polydispersity index (PDI) of 0.181, and mitochondrial uptake was found to be around 91.2 %. The apoptosis score measured following pure-CoQ10 administration was found to be 5.5 times higher compared to DQAsomes, while the inflammation score measured following DQAsomes administration was found to be 6.2 times lower than pure-CoQ10. Overall, these findings suggest promising therapeutic potential for DQAsomes in LS management, emphasizing their role in targeted mitochondrial CoQ10 delivery and potential clinical application. © 2024
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    Enhancement of in-vivo cellular uptake of Coenzyme Q10 using saponin derivatives in rTALAP transgenic mice model
    (Editions de Sante, 2024) Uner B.; Celik A.; Ergin A.D.; Altay Benetti A.; Benetti C.
    Pancreatic cancer remains a significant contributor to cancer-related mortality, with pancreatic ductal adenocarcinoma (PDAC) being particularly challenging to treat. Coenzyme Q10 (CoQ10), a hydrophobic antioxidant crucial for cellular energy production, holds promise in PDAC therapy. However, its limited solubility hinders efficient cellular uptake. To overcome this limitation, we developed micelle formulations incorporating CoQ10 and assessed their potential to enhance cellular delivery. In this particular study, we have utilized some of the most common saponins such as Quillaja saponin, Ginsenoside R0, and Ginsenoside Rb1 as a drug carrier in order to enhance the bioavailability and cellular uptake of CoQ10. Micelles' size and shape were characterized using DLS, TEM, and LC-MS/MS. These all saponin micelles showed better encapsulation, zeta potential, and smaller size compared to Pluronic F127 micelles. Moreover, these formulations induced a notable increase in reactive oxygen species (ROS) generation, indicative of potential apoptotic activity. Further investigations revealed that micelle treatments led to modulation of gene expression related to epithelial-mesenchymal transition (EMT) markers, with an increase in E-cadherin expression and a decrease in claudin, snail, slug, and vimentin. Additionally, in-vivo screening studies in transgenic mice demonstrated promising results as anticancer by reducing apoptosis. In conclusion, our findings suggest that CoQ10-loaded micelles, particularly those incorporating Quillaja saponin and ginsenoside derivatives, hold potential as a novel therapeutic approach for PDAC by enhancing cellular uptake, inducing ROS-mediated apoptosis, and modulating EMT markers. These findings contribute to advancing our understanding of CoQ10's role in pancreatic cancer therapy. © 2024