Drug Targeting Organ-Specific Strategies

11 Development of Proteinaceous Drug
Targeting Constructs Using Chemical and
Recombinant DNA Approaches
Robbert J. Kok, Sigridur A. Ásgeirsdóttir, Willem R. Verweij
11.1 Introduction
Several techniques have been developed to selectively increase the accumulation of drugs in
specific organs and tissues. One of these drug targeting techniques is the covalent conjugation
of the drug to a macromolecule that accumulates at the target site. For this purpose, proteins
as well as various other types of (polymeric) macromolecules can be used as drug carriers.
This chapter will focus on the design and preparation of proteinaceous drug targeting
structures.
Figure 11.1 shows the functional domains that are present in such a drug targeting structure.
The core of the construct is the carrier backbone which, in the case of a proteinaceous
construct, consists of a protein. Among other factors, the size of the carrier protein has a major
influence on the distribution of the drug–carrier construct within the body. More specific
targeting of the construct can be achieved by incorporation of site-directing ligands (homing
devices) into the protein. By binding to specific receptors, the homing device is instrumental
in delivering the construct to its target site.The homing device can be either a conjugated antennary
group, or simply an intrinsic domain of the protein. Finally, an essential part of a drug
homing
device
Drug Targeting Organ-Specific Strategies. Edited by G. Molema, D. K. F. Meijer
Copyright © 2001 Wiley-VCH Verlag GmbH
ISBNs: 3-527-29989-0 (Hardcover); 3-527-60006-X (Electronic)
carrier
protein
biodegradable
linkage
drug
Figure 11.1. General structure of a proteinaceous drug targeting construct. Functional domains present
in a drug targeting construct are (1) the carrier protein, (2) homing devices or site-directing ligands and
(3) the drug moiety. In order to ensure its activation, the drug is often attached via a biodegradable
linkage to the carrier.