The impact of retinol loading and surface charge on the hepatic delivery of lipid nanoparticles.

The present work developed lipid nanoparticles to determine whether retinol loading and surface charge influenced liver targeting and biodistribution. Silibinin for treating liver fibrosis was used as the active model. The capability of nanoparticles to suppress hepatic stellate cells (HSCs) was investigated by examining cell viability and α-smooth muscle actin (α-SMA). The biodistribution of the nanocarriers in rats was monitored by real-time and organ bioimaging after an intravenous injection. Silibinin concentration in the organs was detected as well. Anionic nanoparticles showed a mean size of around 260 nm, which was greater than that of cationic nanoparticles (about 170 nm). The encapsulation percentage of silibinin was >98% for both anionic and cationic nanoparticles. All nanoparticles tested were able to be ingested into HSCs, with no difference between the formulations. The positive nanoparticles produced activated HSC apoptosis much more strongly than negative nanoparticles. The α-SMA suppression exhibited a contrary trend. The nanoparticles rapidly accumulated in the liver and spleen. Retinol incorporation in nanoparticles offers an active targeting approach to the liver via retinol binding protein (RBP). The negatively charged formulation containing retinol achieved higher uptake and longer retention in the liver than the other formulations. Silibinin inclusion in nanoparticles significantly decreased lung deposition and increased liver uptake. The lipid nanosystems promoted silibinin distribution to the liver by 2-3-fold compared to the free control. A better liver-specific selectivity was obtained by retinol-loaded anionic nanocarriers. It is important to optimize the formulations of the lipid nanoparticles for maximizing hepatic targeting.