Curcumin-Zein Nanospheres Improve Liver Targeting and Antifibrotic Activity of Curcumin in Carbon Tetrachloride-Induced Mice Liver Fibrosis

Liver fibrosis is a major health problem that has no satisfactory medication. Curcumin, (CUR) although known for its antifibrotic activity, has limited medicinal use owing to its poor oral pharmacokinetic properties and targeting efficiency. The current study aimed at exploring the ability of zein (ZN) nanospheres to improve the liver targeting and antifibrotic activity of CUR in a mouse model of carbon tetrachloride (CCl₄)-induced liver fibrosis. Four different formulae of ZN-loaded CUR were prepared and examined in terms of particle size, zeta potential, encapsulation efficiency, and in vitro permeation. The formula containing a CUR to ZN ratio of 1:3 showed optimum nanosphere properties and was subjected to further investigations. Under a scanning electron microscope, the selected formula showed spherical particles with uniform size distribution. In normal mice, the selected formula exhibited improved bioavailability and liver targeting efficiency compared to raw CUR. The nanosphere preparation also offered significant protection against CCl₄-induced liver function deterioration, histopathological changes, and oxidative stress in mice. Compared to raw CUR, CUR-ZN was significantly more effective in attenuating the rise in hepatic gene expression of collagen-1, tissue inhibitor of metalloproteinase-2, and transforming growth factor beta, as well as the downregulation of matrix metalloproteinase-2 expression. Masson's trichrome staining confirmed the higher antifibrotic activity of the nanospheres that ameliorated the rise in hepatic hydroxyproline content and collagen-1-immunopositive areas in mice liver sections. In conclusion, CUR-ZN nanospheres demonstrated improved liver targeting efficiency and antifibrotic activity in comparison to raw CUR in CCl₄-induced liver fibrosis in mice.