Simple but novel taxifolin@pro-glycymicelles as effective treatment for acetaminophen overdose-induced hepatotoxicity: preparation, in vitro characterizations, and in vivo experimental evaluations.
Yao Dong, Ling Zhang, Xixi Song, Xiaoli Chen, Yuyan He, Xianggen Wu, Mengshuang Li
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引用次数: 0
Abstract
Objective: To develop a simple but novel formulation named TAX@pro-glycymicelles with glycyrrhizin as the nanomaterial encapsulating taxifolin (TAX).
Significance: TAX@pro-glycymicelles, simply prepared with two generally recognized as safe phytochemicals, demonstrated excellent characteristics, improved oral bioavailability of TAX, and strong effects against hepatotoxicity.
Methods: TAX@pro-glycymicelles were prepared, and its physicochemical properties were determined. Safety assays, oral bioavailability in rats, treatment effects and mechanisms on liver injury in mice were also inflicted on TAX@pro-glycymicelle.
Results: TAX@pro-glycymicelles were simply prepared, and the obtained powder demonstrated good storage stability and could be rapidly solubilized into water solutions to be clear nano-glycymicelle solutions. The apparent aqueous solubility of TAX from TAX@pro-glycymicelles was exceptionally improved to higher than 40 mg/ml. The in vitro release of TAX@pro-glycymicelles was also accelerated, and their in vitro antioxidative activity increased. Hemolysis and hen's egg test-chorioallantoic membrane assays showed that TAX@pro-glycymicelles exhibited good safety profiles. Oral bioavailability of TAX@pro-glycymicelles was approximately 32.1% higher than that of bare TAX in rats. TAX@pro-glycymicelles was also found to have a stronger dose-dependent treatment effect on acetaminophen overdose-induced hepatotoxicity in mice than bare TAX, including decreasing liver-to-body and spleen-to-body weight ratios, significantly decreasing alanine aminotransferase and aspartate aminotransferase levels in serum, decreasing inflammation and oxidative stress cytokine levels in livers, and reversing severe histological damage to liver tissues. The mechanisms of inhibiting oxidative stress and blocking high-mobility group box 1 signaling-related proinflammatory cytokines were involved in these strong treatment effects.
Conclusions: TAX@pro-glycymicelles were found to be promising nano-formulations for treating acetaminophen overdose-induced hepatotoxicity.
期刊介绍：
The aim of Drug Development and Industrial Pharmacy is to publish novel, original, peer-reviewed research manuscripts within relevant topics and research methods related to pharmaceutical research and development, and industrial pharmacy. Research papers must be hypothesis driven and emphasize innovative breakthrough topics in pharmaceutics and drug delivery. The journal will also consider timely critical review papers.
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