Drug Targeting to the Liver

The bile add ursodeoxycholic acid has shown some promise in slowing down the fibrotic process in cholestatic patients, especially those suffering from PBC and PSC [77,78]. Its mechanism of action, however, is stiU a matter of debate. 

Several types of immunosuppression have also been tried. Azathioprine alone was found to have no effect on PBC [82], but additional benificial effects were found in combination with ursodeoxychohc add and corticosteroids [78]. Cyclosporin showed some success, espe-dally in corticosteroid-resistant autoimmune hepatitis [83], but its use is generally considerably hmited by severe side-effects. Corticosteroids were effective in the management of several types of autoimmune chronic active hepatitis [84,85] and in the management of acute al-cohohc hepatitis [86]. Their use, however, has to be brief hi order to minimize side-effects. In the treatment of PBC, corticosteroids alone were found to be toxic and had only limited efficacy [77]. 

4 Cell Specific Delivery of Anti-Inflammatory Drugs to Hepatic Cells 

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Table 16 Targeting of Drugs to the Liver with Glycoproteins and Glycoconjugates...

As mentioned in Section 11.2, a special class of proteinaceous targeting constructs are those in which a therapeutic protein is used as the active drug substance. In such a preparation, the protein is redirected to the target tissue by the attachment of site-directing ligands such as those discussed in Section 11.3. For instance, interferon beta (IFN- 3) can be redirected to the liver by enz5matic desialylation in a procedure similar to that described earlier for fetuin (Section 11.3.1). The resultant asialo-IFN- 3 was found to have an in vivo anti-viral effect when tested in a hepatitis B model in athymic nude mice [54]. 

L. Fiume, C. Busi, G. Di Stefano, and A. Mattioli, Targeting of antiviral drugs to the liver using glycoprotein carriers, Adv. Drug Deliv. Rev. 14 51 -65 (1994). 

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