Hepatic macrophages have been considered as a therapeutic target for
liver fibrosis treatment, and
phosphatidylserine (PS)-containing nanoparticles are commonly used to mimic apoptotic cells that can specifically regulate macrophage functions, resulting in anti-inflammatory effects. This study was designed to test the efficacy of PS-modified nanostructured
lipid carriers (mNLCs) containing
curcumin (Cur) (Cur-mNLCs) in the treatment of
liver fibrosis in a rat model.
Carbon tetrachloride-induced
liver fibrosis in rats was used as an experimental model, and the severity of the disease was examined by both biochemical and histological methods. Here, we showed that mNLCs were spherical nanoparticles with decreased negative zeta potentials due to PS decoration, and significantly increased both mean residence time and area under the curve of Cur. In the rats with
liver fibrosis, PS-modification of NLCs enhanced the nanoparticles targeting to the diseased liver, which was evidenced by their highest accumulation in the liver. As compared to all the controls, Cur-mNLCs were significantly more effective at reducing the liver damage and
fibrosis, which were indicated by in Cur-mNLCs-treated rats the least increase in liver
enzymes and pro-inflammatory
cytokines in the circulation, along with the least increase in
collagen fibers and alpha smooth muscle actin and the most increased hepatocyte
growth factors (HGF) and matrix
metalloprotease (
MMP) two in the livers. In conclusion, PS-modified NLCs nanoparticles prolonged the retention time of Cur, and enhanced its bioavailability and delivery efficiency to the livers, resulting in reduced
liver fibrosis and up-regulating hepatic expression of HGF and MMP-2.