Aim To investigate the release feature of ginsenoside Rd solid lipid nanoparticles (Rd-SLN) in vitro,and to clarify the difference in absorption of Rd-SLN from varied rat intestinal segments and pharmacokinetic properties in vivo. Methods Dialysis method was used to determine ginsenoside Rd release rate from nanoparticles in vitro. Perfusion method was used to study the intestinal absorption of Rd-SLN in rat. HPLC assay was established to determine the concentration of ginsenoside Rd in plasma. After intragastric administration,the concentrations of drug in rat blood at different time points were recorded to investigate the absorption and pharmacokinetics of Rd-SLN. Results The release of ginsenoside Rd from Rd-SLN was slowed down and presented the property of sustained release. There was no significant difference between the absorption rate of Rd-SLN and control solution in duodenum and jejunum. However,it was obviously different in ileum and colon. Comparing with other intestinal segments,significantly higher percentage of Rd-SLN was absorbed in colon. In Rd-SLN group,the concentration of ginsenoside Rd in blood was maintained,and the Cmax,MRT,AUMC,and AUC were all increased. Conclusions Rd-SLN possesses sustained-release effect. The colon is the preferable absorption site for Rd-SLN in intestinal tract. Rd-SLN can enhance the oral bioavailability of ginsenoside Rd.

Arsenic trioxide (AsO) is recently found to have therapeutic potential in systemic sclerosis (SSc), a life-threatening multi-system fibrosing autoimmune disease with type I interferon (IFN-I) signature. Chronically activated plasmacytoid dendritic cells (pDCs) are responsible for IFN-I secretion and are closely related with fibrosis establishment in SSc. In this study, we showed that high concentrations of AsO induced apoptosis of pDCs mitochondrial pathway with increased BAX/BCL-2 ratio, while independent of reactive oxygen species generation. Notably, at clinical relevant concentrations, AsO preferentially inhibited IFN- secretion as compared to other cytokines such as TNF-, probably due to potent down-regulation of the total protein and mRNA expression, as well as phosphorylation of the interferon regulatory factor 7 (IRF7). In addition, AsO induced a suppressive phenotype, and in combination with cytokine inhibition, it down-regulated pDCs' capacity to induce CD4 T cell proliferation, Th1/Th22 polarization, and B cell differentiation towards plasmablasts. Moreover, chronically activated pDCs from SSc patients were not resistant to the selective IFN- inhibition, and regulatory phenotype induced by AsO. Collectively, our data suggest that AsO could target pDCs and exert its treatment efficacy in SSc, and more autoimmune disorders with IFN-I signature.