Development and Evaluation of a Water-in-oil Microemulsion Formulation for the Transdermal Drug Delivery of Teriflunomide (A771726).

Teriflunomide (TEF, A771726) is the active metabolite of leflunomide (LEF), a disease-modifying anti-rheumatic drug. The main purpose of this study was to develop and evaluate water-in-oil (W/O) microemulsion formulation of TEF. The W/O microemulsion was optimized formula is the physical and chemical stability of lecithin, ethanol, isopropyl myristate (IPM) and water (20.65/20.78/41.52/17.05 w/w) by using the pseudo-ternary phase diagram and the average droplet size is about 40 nm. The permeability of TEF microemulsion is about 6 times higher than control group in vitro penetration test. The results of anti-inflammatory effect showed that compared with the control group, the external TEF microemulsion group could significantly inhibit swelling of paw in rats, and no significant difference compared with oral LEF group. The results of hepatotoxicity test show that there were normal content of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and no obvious inflammatory infiltration of TEF microemulsion group compared with LEF group. The plasma concentration curve showed that compared with LEF group, the peak concentration of TEF microemulsion group was decreased, the half-life (t1/2) was prolonged, and the relative bioavailability of TEF microemulsion was 75.35%. These results suggest that TEF W/O microemulsion can be used as a promising preparation to play an anti-inflammatory role while significantly reducing hepatotoxicity.

Rosiglitazone protects rat liver against acute liver injury associated with the NF-κB signaling pathway.

Rosiglitazone, which is mainly used in the treatment of diabetes mellitus, is also involved in the regulation of inflammation. The peroxisome proliferator-activated receptor (PPAR)-γ receptor subtype appears to play a pivotal role in the regulation of inflammation. However, the exact mechanism for the protective effects of rosiglitazone against inflammation such as liver injury remains unclear. The aim of this study was to investigate the effects of rosiglitazone on inflammation in the liver of rats treated with D-GaIN/LPS. Male Sprague-Dawley rats were injected with D-GaIN/LPS with or without pre-administration of rosiglitazone (3, 10, or 30 mg/kg, intraperitoneal injection). Our data showed that rosiglitazone significantly inhibited D-GaIN/LPS-induced hepatotoxicity in a dose-dependent manner, as indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Western blot analysis showed that rosiglitazone significantly decreased protein expression levels of COX-2 and production of pro-inflammatory markers, including TNF-α and IL-6, in D-GaIN/LPS-treated rat liver. The results indicated that the inhibition of D-GaIN/LPS-induced inflammation by rosiglitazone can be attributed, at least partially, to its capacity to regulate the the immunoregulatory transcription factor nuclear factor kappa B (NF-κB) signaling pathway.