Enhanced efficacy of curcumin with phosphatidylserine-decorated nanoparticles in the treatment of hepatic fibrosis

Drug Delivery

Caigan Du¹  Wen Pan²  Bin Feng²  Wan Lei²  Xiao-juan Wang²  Ying Wang²  Ji Wang² 

[1] Department of Urologic Sciences, University of British Columbia, Jack Bell Research Centre, Vancouver, BC, Canad;State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University, Xi’an, PR China;

关键词: Phosphatidylserine;    curcumin;    nanostructured lipid carriers;    liver fibrosis;    macrophages;   

DOI  :  10.1080/10717544.2017.1399301

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY