TARGETING OF ANTIVIRAL DRUGS TO THE LIVER USING GLYCOPROTEIN CARRIERS

In order to improve the efficacy and to reduce the side-effects of antiviral drugs in the treatment of chronic hepatitis B, a lysosomotropic approach through covalent linkage of the drugs to appropriate glycoproteins was adopted. Antiviral nucleoside analogs were coupled to asialofetuin and to lactosaminated albumin (L-SA) (two galactosyl-terminating glycoproteins). The conjugates were selectively taken up by liver cells where they released the drugs in a pharmacologically active form. L-SA conjugates showed the advantage of being non-immunogenic when prepared with homologous albumin and injected intravenously. The majority of the experiments reported in this article were performed employing a conjugate of L-SA with ara-AMP, a drug active against hepatitis B virus (HBV). The results of animal studies warranted a 7-day administration of L-HSA-ara-AMP to patients with chronic hepatitis B. Conjugated ara-AMP was shown to inhibit HBV growth at a dose 3-6 times lower than that of the free drug.