Enhancement of in-vivo cellular uptake of Coenzyme Q10 using saponin derivatives in rTALAP transgenic mice model
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Tarih
2024
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Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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
Açıklama
Anahtar Kelimeler
Adenocarcinoma; Coenzyme Q10; Pancreatic Cancer; Ros; Saponin Micelle, Claudin; 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 Potential
Kaynak
Journal of Drug Delivery Science and Technology
WoS Q Değeri
Scopus Q Değeri
Q1
Cilt
96
