Targeting of naproxen covalently linked to HSA to sinusoidal cell types of the liver

We have coupled the anti-inflammatory drug naproxen (Nap) covalently to human serum albumin (HSA) to deliver this drug selectively to non parenchymal cell types of the liver during endotoxin induced hepatic inflammation. Liver endothelial cells and Kupffer cells play an important role in the pathogenesis of acute and chronic inflammatory liver diseases. Targeting Nap to these cells might increase the efficacy of this drug in the treatment of these diseases and reduce its side effects. During acute inflammation in male rats, induced by endotoxin, livers showed an increased uptake of Nap when coupled to HSA as compared to free Nap. 3 hours after administering 24 mg/kg Nap(23)-HSA 28% of the dose was found in the liver versus 1.1% of a therapeutic dose of 50 mg/kg Nap (p In conclusion, during endotoxin induced inflammation the distribution of Nap as a Nap(23)-HSA conjugate to the liver is enhanced as compared to free Nap. Moreover, Nap liberated from the albumin carrier by proteolytic degradation exhibits a longer residence time in the liver, as compared to free Nap.