TARGETING OF DRUGS TO VARIOUS BLOOD-CELL TYPES USING (NEO-)GLYCOPROTEINS, ANTIBODIES AND OTHER PROTEIN CARRIERS

The current problems in controlling severe viral infections of blood cells such as in AIDS as well as the lack of effective and safe pharmacotherapeutic measures for such diseases have renewed interest in the options of targeting of drugs and genes to various blood cell types. The design and development of potential carriers for cell-specific delivery of therapeutics should be based on the knowledge of recognition sites on the surface of blood cells as well as on insight into the internalization and further cellular disposition of such macromolecules. In this review the presence of various lectins on T-lymphocytes and monocytes/macrophages as well as immunological receptors and adhesion molecules is described. These recognition sites could in principle serve in binding and/or endocytosis of glycoconjugate carriers for the delivery of drugs and genetic material. Glycoproteins with a suitable density of sugar groups or a proper geometric organization of oligosaccharide side-chains may provide potential carriers that escape receptor-mediated endocytic processes in other tissues such as liver, spleen and bone marrow. Other modalities are recombinant T-cell receptors (sCD4) that bind to HIV-infected cells, monoclonal antibodies raised against viral envelope proteins, and certain cytokines. Bacterial toxins, antisense DNA and genes that code for synthesis of antivirally active proteins as well as coupling products of nucleoside analogs such as AZT have been delivered to blood cells using this technology. Some of these drug carriers may provide an intrinsic antiviral action that may add to the effect of the coupled drug (dual targeting). Such multi-active drug targeting preparations may offer the advantages of synergistic effects and counteraction of drug resistance apart from the improved body distribution aimed at. More detailed in vivo studies should be performed in patients to test the promising concepts that have been developed in in-vitro studies. It is obvious that such preparations should have major advantages compared with the untargeted material to compensate for the intrinsic drawback of parenteral administration