Design, Preparation, and Characterization of Dioscin Nanosuspensions and Evaluation of Their Protective Effect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Abstract

The purpose of this study was to prepare a dioscin nanosuspension (Dio-NS) that has a better distance and high solubility for oral administration and to evaluate its hepatoprotective effects. Optimal primary manufacture parameters, including shear time, shear speed, emulation temperature, pressure, and cycles of homogenization, were determined by single-factor experiments. The concentrations of dioscin, SDS, and soybean lecithin were optimized using the central composite design-response surface method, and their effects on the mean particle size (MPS) and particle size distribution of Dio-NS were investigated. Characterization of the Dio-NS formulations included examinations of the surface morphology and physical status of dioscin in Dio-NS, the stability of Dio-NS at different temperatures, in vitro solubility, and liver protective effect in vivo. Under optimal conditions, Dio-NS had an MPS of 106.72 nm, polydispersity index of 0.221, and zeta potential of −34.27 mV. Furthermore, the proportion of dioscin in Dio-NS was approximately 21.26%. The observation of particles with a spherical shape and the disappearance of crystalline peaks indicated that the physical and chemical properties of Dio-NS were altered. Furthermore, we observed that the dissolution of Dio-NS was superior to that of a physical mixture and Dio-GZF. Moreover, Dio-NS was demonstrated to have a protective effect against CCl4-induced acute liver damage in mice that was equivalent to that of silymarin (a positive control drug) at the same dose. The good hepatoprotective effect of our Dio-NS preparation can provide a theoretical basis for investigating its absorption mechanisms in the body.

Dioscin: A review on pharmacological properties and therapeutic values

“…116,141 6.1.1 | Acute liver damage More than half of all acute liver injuries are caused by adverse drug reactions, or certain toxic chemicals or drugs such as carbon tetrachloride (CCl 4 ), alphanaphthyl-isothiocyanate (ANIT), dimethylnitrosamine (DMN), paracetamol, and lipopolysaccharide (LPS). 116,141 CCl 4 , ANIT, DMN, LPS, and ethanol have been used in in vitro models to monitor the activity of different medications against acute liver damage. Multiple studies have confirmed the role of dioscin in reducing the serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) to improve liver conditions via the effects of dioscin in ameliorating oxidative stress, inflammation, and apoptosis.…”

“…The liver is a major organ in the human body and it plays a critical role in regulating synthetic and metabolic processes such as detoxification and assimilation. It can be frequently exposed to extreme stress and undergo pathological changes in response to the stress, which may lead to potentially life‐threatening liver damage, 106 including diseases such as hepatitis, fibrosis, cirrhosis, cholestasis, HCC, hepatic ischemia, or other injuries that result in hepatic disorders and acute or chronic liver failure 116,141 …”

“…Moreover, the nanosuspension helped enhance the concentration of dioscin in the blood, thus increasing the efficacy of the drug. This study presents new pharmacological avenues to explore, to develop suitable clinical applications of dioscin formulations that show high efficacy 141 …”

“…More than half of all acute liver injuries are caused by adverse drug reactions, or certain toxic chemicals or drugs such as carbon tetrachloride (CCl 4 ), alpha‐naphthyl‐isothiocyanate (ANIT), dimethylnitrosamine (DMN), paracetamol, and lipopolysaccharide (LPS) 116,141 …”

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“…Liver disease is common and often life-threatening. 1 Carbon tetrachloride (CCl 4 ), 2 paracetamol 3 and lipopolysaccharide 4 may cause acute liver injury. The occurrence of liver injury may be related to viral infection, alcohol and drugs.…”