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

Hong-Ye Ju,Xiao Song,Kun-Xia Hu,Zhi-Shu Tang,Guo-Wang Zhao

doi:10.1155/2019/3907915

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.

Highlights

Dioscin (Figure 1), known as Paris polyphylla saponin III, is a steroidal saponin [1]that can be extracted from the Chinese yam (Dioscorea paniculata) and other plants in the Dioscoreaceae family [2]
We found that when the combined application of soybean lecithin and sodium alkyl sulfate twelve (SDS) was used as a stabilizer for the suspension system, the average size of the drug particles was small, the distribution was narrow, and the physical stability of the system was good. erefore, we used soybean lecithin and SDS as stabilizers for Dioscin differential scanning calorimeter (DSC) (Dio)-NS
We have demonstrated that nanosuspensions can be successfully prepared using an emulsification method in which high-speed homogenization is used in combination with high-pressure homogenization, which is better than previously prepared drug formulations [32, 33]

Summary

Introduction

Dioscin (Figure 1), known as Paris polyphylla saponin III, is a steroidal saponin [1]that can be extracted from the Chinese yam (Dioscorea paniculata) and other plants in the Dioscoreaceae family [2]. Dioscin has several important pharmacological activities, including antitumor [3], antiinflammatory [4], antiliver damnification [5], antihepatic fibrosis [6, 7], antihyperlipidemic, and antioxidative properties. The compound has therapeutic potential in metabolic diseases and can be decomposed into diosgenin, which has been an important basic raw material for the production of steroid hormone drugs [8].it has been established that there is potential to develop the pharmaceutic value of dioscin. Some reports have been found on dioscin toxicology. It has no adverse effect on the acute toxicological studies at a dose of 562.5 mg/ kg/d in mice [9, 10]. Rational drug use is the key to lower ADR

Methods

Results

Discussion

Conclusion