ABSTRACT
Acute liver failure is an uncommon and dramatic clinical syndrome with a high risk of mortality. Previous treatments existed some limitations of poor bioavailability and targeting the efficiency of drugs. In this study, a novel glycyrrhizin mediated liver-targeted alginate nanogels, which can deliver the antioxidant quercetin to the liver for the treatment of acute liver injury. In vitro radical scavenging results showed that the antioxidant activity of quercetin was increased 81-fold. The tissue distribution results indicated that glycyrrhizin-mediated nanogels showed stronger fluorescence intensity in the liver, which improved liver targeting and therapeutic efficacy. Quercetin-glycyrrhizin nanogels were more effective at restoring liver injury as indicated on serum markers, including alanine transaminase, aspartate aminotransferase, and total bilirubin. The histopathology result showed that quercetin-glycyrrhizin nanogels reversed liver damage. Oxidative parameters of malondialdehyde and glutathione s-transferase were decreased, which provided supporting evidence of antioxidation. Moreover, quercetin-glycyrrhizin nanogels were more effective in down-regulating the inflammation-related gene expression of tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase and monocyte chemotactic protein-1. In conclusion, the novel glycyrrhizin mediated liver-targeted alginate nanogels might be a promising treatment for acute liver failure.
Subject(s)
Alginates/chemistry , Glycyrrhizic Acid/metabolism , Quercetin/administration & dosage , Alanine Transaminase/blood , Alginates/pharmacology , Animals , Antioxidants/pharmacology , Aspartate Aminotransferases/blood , Chemical and Drug Induced Liver Injury/pathology , China , Glycyrrhizic Acid/chemistry , Inflammation/drug therapy , Liver/drug effects , Liver Failure, Acute/metabolism , Male , Mice , Nanogels/administration & dosage , Nanogels/chemistry , Nitric Oxide Synthase Type II/metabolism , Oxidative Stress/drug effects , Quercetin/pharmacology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Injectable hydrogels have been paid more attentions on cell therapy and tissue regeneration resulting from the applications in minimally invasive surgical procedures with ease of handling and complete filling of defect area. Here, a biodegradable and injectable in situ hydrogel formed by glycyrrhizin (GL), alginate (Alg), and calcium (Ca) was developed for three-dimensional (3D) cell culture. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscope (SEM) and rheology analysis were performed to characterize GL-Alg-Ca hydrogel and evaluate its formation mechanism, properties, and morphology. The biocompatibility of hydrogel was investigated by cell viability, morphology, and liver specific functions. The results of DSC, XRD, and rheology suggested that hydrogel was homogenous complex with stable structure and well viscoelasticity. Human hepatoma HepG2 cells cultured in hydrogels showed well morphology. Compared with the control group, cells in hydrogels showed good biocompatibility, and could maintain the viability, proliferation and liver function for longer periods of time. Furthermore, the hydrogel improved the mRNA expression of cytochrome P450, which were key enzyme to the metabolization of hepatocytes. The GL-Alg-Ca hydrogel could be a potential 3D cells culture system for liver tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3292-3302, 2018.
