Enhancement of in-vivo cellular uptake of Coenzyme Q10 using saponin derivatives in rTALAP transgenic mice model

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dc.authorscopusid57302092900
dc.authorscopusid57283760100
dc.authorscopusid57396839700
dc.authorscopusid57726915100
dc.authorscopusid57190986086
dc.contributor.authorUner B.
dc.contributor.authorCelik A.
dc.contributor.authorErgin A.D.
dc.contributor.authorAltay Benetti A.
dc.contributor.authorBenetti C.
dc.date.accessioned2024-06-12T10:25:02Z
dc.date.available2024-06-12T10:25:02Z
dc.date.issued2024
dc.description.abstractPancreatic 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. © 2024en_US
dc.description.sponsorshipUniversity of Washington, UW; 03-2812en_US
dc.description.sponsorshipWe are grateful for the invaluable support provided by the Animal Diagnostic Lab (Protocol no: 03-2812) and Anesthesiology and Pharmacology Research Center Lab at Washington University. Their unwavering assistance was paramount in the successful completion of this research project.en_US
dc.identifier.doi10.1016/j.jddst.2024.105636
dc.identifier.issn1773-2247
dc.identifier.scopus2-s2.0-85190729503en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.jddst.2024.105636
dc.identifier.urihttps://hdl.handle.net/20.500.14551/16164
dc.identifier.volume96en_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherEditions de Santeen_US
dc.relation.ispartofJournal of Drug Delivery Science and Technologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAdenocarcinoma; Coenzyme Q10; Pancreatic Cancer; Ros; Saponin Micelleen_US
dc.subjectClaudin; Drug Carrier; Ginsenoside R0; Ginsenoside Rb 1; Poloxamer; Quillaja Saponin; Reactive Oxygen Metabolite; Saponin Derivative; Succinic Acid; Tamoxifen; Transcription Factor Slug; Transcription Factor Snail; Ubidecarenone; Unclassified Drug; Uvomorulin; Vinculin; Animal Experiment; Animal Model; Animal Tissue; Antineoplastic Activity; Apoptosis; Article; Carcinogenesis; Cell Metabolism; Cell Viability; Controlled Study; Copy Number Variation; Drug Bioavailability; Drug Delivery System; Drug Formulation; Drug Uptake; Encapsulation; Epithelial Mesenchymal Transition; Gene Expression Level; Gene Expression Regulation; Gene Mapping; Genetic Modification; Hpde6c7 Cell Line; Human; Human Cell; Ic50; In Vitro Study; In Vivo Study; Intracellular Signaling; Limit Of Detection; Limit Of Quantitation; Mitochondrial Membrane Potential; Mouse; Nanoemulsion; Nonhuman; Pancreatic Ductal Carcinoma; Particle Size; Protein Expression; Quantitative Analysis; Sustained Drug Release; Zeta Potentialen_US
dc.titleEnhancement of in-vivo cellular uptake of Coenzyme Q10 using saponin derivatives in rTALAP transgenic mice modelen_US
dc.typeArticleen_US

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