A major function of the intrahepatic biliary epithelium is
bicarbonate excretion in bile. Recent reports indicate that
budesonide, a
corticosteroid with high receptor affinity and hepatic first pass clearance, increases the efficacy of
ursodeoxycholic acid, a choleretic agent, in
primary biliary cholangitis patients. We have previously reported that bile ducts isolated from rats treated with
dexamethasone or
budesonide showed an enhanced activity of the Na+/H+ exchanger isoform 1 (NHE1) and
Cl-/HCO3- exchanger protein 2 (AE2) . Increasing the delivery of
steroids to the liver may result in three beneficial effects: increase in the choleresis, treatment of the autoimmune or inflammatory liver injury and reduction of
steroids' systemic harmful effects. In this study, the
steroid dexamethasone was loaded into nanohydrogels (or
nanogels, NHs), in order to investigate
corticosteroid-induced increased activities of transport processes driving
bicarbonate excretion in the biliary epithelium (NHE-1 isoform) and to evaluate the effects of
dexamethasone-loaded NHs (NHs/dex) on liver injury induced by experimental cholestatis. Our results showed that NHs and NHs/dex do not reduce cell viability in vitro in human cholangiocyte cell lines. Primary and immortalized human cholangiocytes treated with NHs/dex show an increase in the functional marker expression of NHE1 cholangiocytes compared to control groups. A mouse model of cholangiopathy treated with NHs/dex shows a reduction in markers of hepatocellular injury compared to control groups (NHs, dex, or
sham group). In conclusion, we believe that the NHs/dex formulation is a suitable candidate to be investigated in preclinical models of cholangiopathies.