Preparation And Characterization Of Dehydrosilybin Phospholipid Complex-liposomes

Dehydrosilybin(DHS) is a 2,3-dehydro derivative of silybin. Research showed that, in comparison to silybin, DHS has better superior antioxidant and radical scavenging capacity, stronger anti-tumor property. However, its clinical use has been limited due to its low aqueous solubility and liposolubility, which resulted in poor oral absorption. Preparation of drug-phospholipid complex is commonly used to improve its lipophilicity. In order to further improve the solubility of dehydrosilybin in water,an improve injection method were emploved preparing homogeneously dispersed and stable dehydrosilybin-phospholipid complex phyto-lipsome with small particle size,and high encapsulation efficiency.First, well dispersed dehydrosilybin was synthesized by air oxidation process, and’H NMR spectra analysis was used to comfirm the structure of dehydrosilybin.Next, the DHS-phospholipid complex was prepared to improve its liposolubility. The optimal reaction parameters were as follows:solvent was acetone; the solvent in an amount of 20 ml; the best drug to lipid molar ratio was 1:1; the best reaction time was 3h. And the yield and recombination rate were 97.6% and 86%, respectively.To further investigate the physicochemical property, we measured the different solubilities in water and n-octyl alcohol of dehydrosilybin and dehedrosilybin-phospholipid complex in indoor temperature. The results of aqueous solubilities were 2.846±0.186 μg/ml and 14.023±1.014 μg/ml, respectively. Meanwhile the solubilities in n-octyl alcohol respectively were 0.528±0.028 μg/ml,1.0169±0 μg/ml. In Contrast with the solubilities of silybin and silybin-phospholipid complex,the results showed that dehydrosilybin has poor solubility to that of silybin. However, comparing with the silybin-phospholipid complex, the dehydrosilybin-phospholipid complex had a similar solubility in water, much better in n-octyl alcoho.To improve the bioavailability of dehydrosilybin, we prepared dehydrosilybin-phospholipid complex phyto-liposomes. The effects of experimental condition such as different preparation methods, solvent volume, ultrasound time, phospholipid complex with phospholipids weight ratio on average partical size and encapsulation efficiency was examined. The results showed that the optimal preparation condition were as followed: adopt the improved injection method, ethanol/ether(v/v=1:1)mixed solvent, phospholipid concentration 6 mg/mL, ultrasonic 2min, weight ratio of 1:6. The characteristics and qualities of liposomes were evaluated,including:average particle diameter 215±2.3 nm, PdI 0.3± 0.026, encapsulation efficiency 96.4%, zeta potential -21.8±0.5. The amount of dehydrosilybin encapsulated in liposomes was 381.3 μg/ml.