Drug Targeting Organ-Specific Strategies

4 1 Drug Targeting: Basic Concepts and Novel Advances
1.2.3 Modified (Plasma) Proteins
Modified plasma proteins are attractive carriers for drug targeting as they are soluble molecules
with a relatively small molecular weight. They can easily be modified by covalent attachment
of peptides [10] (see Figure 1.2), sugars [11,12], and other ligands, as well as drugs
of interest. Particularly in the case of liver cell targeting, quite extensive modifications of protein
backbones such as albumins have been carried out. The carriers and drug–carrier conjugates
rapidly distribute to either the hepatocytes and/or the non-parenchymal cells, depending
on the net protein charge and hydrophobicity. If the target cells are, however, for example
tumour cells or vascular endothelial cells in tumours or inflammatory lesions, rapid distribution
to the liver is an undesirable characteristic. As a consequence, only minor modifications
are allowed in the protein backbone [13], which may pose a serious drawback in using
these proteins for non-hepatic drug targeting.
Figure 1.2. A novel strategy in the development of cell-specific carriers consists of the identification of
a stretch of amino acids/peptides within a cytokine molecule that is specific for receptor binding. These
peptides can serve as homing ligands for a macromolecular protein by covalent attachment to the
protein backbone. The resulting carrier can subsequently be conjugated with drug molecules. Besides
delivering the drug at or into the target cells, carrier or conjugate binding to the cytokine receptor may
be able to inhibit or induce activation of signal transduction pathways. Adapted from Beljaars L, thesis
Groningen University (1999) and reference [10].
1.2.4 Soluble Polymers
Soluble synthetic polymers have been widely employed as versatile drug carrier systems.
Polymer chemistry allows the development of tailor made conjugates in which target moi-