Pharmacokinetic/Pharmacodynamic Determinations of Iron-tannic Molecular Nanoparticles with its Implication in MR Imaging and Enhancement of Liver Clearance.

Abstract

Assessment and enhancement of liver clearance are promising strategies for protection of liver from various liver diseases. Iron-tannic nanoparticles (FTs) were previously considered as imageable autophagic enhancers with biodegradation potential. Herein, we present a new approach for utilizing Iron-tannic nanoparticles (FTs) as a tool for imaging and increasing liver clearance. Pharmacokinetic profiling suggested that FTs were initially found in blood circulation and thereafter were distributed to the liver. By using MR imaging (T1 weighted), maximum MRI signal enhancement was found to occur after 30 minutes post-injection (i.v.) and gradually decreased afterward. Decreasing MRI signal may be due to FTs metabolism by the liver. By assessing imaging-derived pharmacokinetics, we can simply determine the rate constant of liver degradation of FTs. Potentially, we might use this parameter to monitor liver function, where its clearance is of concern. Once functional implication of FTs in liver clearance was investigated, FTs were found to induce hepatocyte autophagy along with activation of lysosomes. Consequently, the hepatocytes were capable of efficiently clearing cellular debris. From these results, it is clear that FTs should be considered as a molecular tool for quantitative MRI-derived liver function assessment, and for enhancing clearance function in liver parenchyma. Hopefully, our findings will pave the way to develop new strategies for non-invasive assessment and enhancement of liver clearance.