Abstract
The unmet medical needs related to liver fibrosis and its incurable effects bring to an urgent necessity to find new treatment strategies from which, nutra-pharmaceuticals and nanotechnology are attracting a considerable interest. The natural flavonoid, quercetin and the essential oil of fennel were proposed for their proven antifibrotic activity. They were successfully loaded in lipid nanocapsules, which were furtherly coated with hyaluronic acid for enhanced CD44active targeting potential. Thorough in vitro optimization produced monodisperse nanocapsules (particle size; 36.78 nm and PDI <0.2). Coating with hyaluronic acid not only sustain quercetin release but also, induce an efficient time dependent accumulation in a highly CD44 expressing cell line, HepG2, opposite to the uncoated nanocapsules. lipid nanocapsules coated with hyaluronic acid and loaded with both quercetin and fennel oil proved a promising synergistic antifibrotic efficiency on rats with CCL4-induced liver fibrosis. In vivo results revealed a significant improvement in liver function tests along with a significant reduction in liver fibrosis markers. Based on the significant downregulation in both liver oxidative stress parameters and hepatic proinflammatory cytokines, mechanism of action can be elucidated to be through antioxidant enzymes activation and inhibition of inflammatory mediators. Concerning toxicity, no reported hematological, hepato-or nephrotoxicity with all formulations, guaranteeing their safety. Hence, tried combination holds a promising treatment to liver fibrosis.
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