Liver uptake & ADMET studies

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Challenge

Due to its extremely active blood clearance function, the liver is often a challenge for the bioavailability of biologics and nanopharmaceuticals. 

Did you know that the hepatocytes are most often not the major cell type responsible for liver metabolism of these compounds?

As the figure above illustrates, hepatocytes (Hep) surround the liver capillaries (sinusoids), that are lined mainly by liver sinusoidal endothelial cells  (LSEC) and Kupffer cells (KC). A fourth cell type, the stellate cell (shown in lilac), lies between the sinusoidal lining and the hepatocytes. LSEC and KC are responsible for most of the liver uptake of blood borne large molecules and particles (green corpuscles).

Hepatocytes make up more than 90 % of the liver volume whereas LSECs and KCs, collectively referred to as scavenger cells, represent only a minute part of the liver mass, but yet make up about a third of the cell number. 

Constituting a surface area of 150 m2 in a normal human liver, the scavenger cells are optimally located and shaped to surveil the contents of the large amounts of blood that pass through the liver vasculature.

Any molecule recognized by these cells as foreign will be effectively endocytosed and metabolized.