Phytosome-nanosuspensions for silybin-phospholipid complex with increased bioavailability and hepatoprotection efficacy.

Silybin, a natural compound for treating liver disease, has been shown to provide diverse biological activities such as anticancer, antioxidant and hepatoprotective. However, it is still challenging to develop silybin product due to its poor aqueous solubility and limited gastrointestinal absorption. In order to improve the low bioavailability of silybin, a novel formulation of phytosome-nanosuspensions for silybin shielding termed as SPCs-NPs, has been developed herein for hepatoprotection efficacy. We found that SPCs-NPs formulation not only possessed an increased in vitro dissolution rate but also improved plasma concentration in the in vivo pharmacokinetic study. Moreover, SPCs-NPs was provided with more potent hepatoprotective effects in pharmacodynamic assessments. Moreover, physicochemical features including interactions between silybin and phospholipid, and crystalline variation of the optimized SPCs-NPs formulation were confirmed by using Fourier-transform infrared spectrometry (FTIR), 1H nuclear magnetic resonance spectroscopy (H-NMR), differential scanning calorimetry (DSC), and powder X-ray diffraction spectroscopy (PXRD) respectively. Overall, the interesting finding of this study suggested that SPCs-NPs could be applied as a promising formulation for a higher drug bioavailability and better hepatoprotection efficacy.

Liver Targeting Albumin-Coated Silybin-Phospholipid Particles Prepared by Nab™ Technology for Improving Treatment Effect of Acute Liver Damage in Intravenous Administration.

In this study, a novel human serum albumin nanoparticle loading silybin-phospholipid complex (SLNPs) was developed for liver targeting after intravenous administration. The preparation of the drug delivery system consisted of two steps; initially, a silybin-phospholipid complex (SLC) was produced to improve the lipophilicity of SLB to then achieve enhanced encapsulation of SLB in albumin nanoparticles. FT-IR and XRD analysis confirmed the successful formation of SLC. The complex ratio of SLC in the first step was 99.6%. The encapsulation efficiency and drug loading of SLNPs in the second step were 96.2% and 5.6%, respectively. SLNPs were spherical and well-dispersed, with a zeta potential of approximately - 10 mV, and a mean particle size around 200 nm. An in vivo tissue distribution experiment and a pharmacodynamic experiment showed that, compared with SLB solution, SLNPs had an improved SLB accumulation in the liver. The hepatoprotective effect of SLNPs on CCl4-induced acute liver damage was evaluated. CCl4-damaged mice showed an increased enzymatic activity of ALT and AST; however, enzyme levels returned to near-normal levels in high-dose SLNP-treated mice. As SLNPs combine the enhanced oil solubility of SLC and the passive targeting of albumin nanoparticles, they possess great potential for the treatment of acute liver damage.

[Experimental study of silybin-phospholipid complex intervention on amiodarone-induced fatty liver in mice].

Objective: To probe into the mechanism and interventional effects of silybin-phospholipid complex on amiodarone-induced steatosis in mice. Methods: Eight-week-old male C57BL/6 mice were divided into three groups (5 mice in each group): a control group (WT) with normal diet, a model group with amiodarone 150mg/kg/d by oral gavage (AM), and an intervention group on amiodarone 150mg/kg/d combined with silybin-phospholipid complex(AM+SILIPHOS. All mice were fed their assigned diet for one week. Then, one week later, serum alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol and high-density lipoprotein were detected of each group. A liver pathological change was observed by oil red O and H&E staining. Ultrastructural pathological changes of hepatocytes were observed to evaluate the intervention effect by transmission electron microscopy. RT-q PCR was used to detect the expression of peroxisome proliferator-activated receptor alpha and its regulated lipid metabolism genes CPTI, CPTII, Acot1, Acot2, ACOX, Cyp4a10 and Cyp4a14 in liver tissues. Intra-group comparison was done by paired t-test. One-way ANOVA was used for comparison between groups and semi-quantitative data were tested using Mann-Whitney U test. Results: Oil Red O and H&E staining results of liver tissue in the intervention group showed that intrahepatic steatosis was significantly reduced when compared to model group. Transmission electron microscopy showed that the model group had pyknotic nuclei, mitochondrial swelling, structural damage, and lysosomal degradation whereas the intervention group had hepatic nucleus without pyknosis, reduced mitochondrial swelling and slight structural damage than that of model group. RT-q PCR results showed that the expression of peroxisome proliferator-activated receptor alpha, CPTI, CPTII, Acot1, Acot2, ACOX, Cyp4a10 and Cyp4a14 were increased in the model group but the expression of CPTI, Cyp4a14, Acot1 and peroxisome proliferator-activated receptor alpha were decreased in the intervention group (P < 0.05). Conclusion: Silybin-phospholipid complex can alleviate amiodarone-induced steatosis, and its mechanism may play a role in protecting mitochondrial function and regulating fatty acid metabolism. Thus, silybin-phospholipid complex has potential intervention effect on amiodarone-induced fatty liver.