Targeting moiety

In macromolecular dmg delivery systems, dmgs are attached to polymeric compounds, such as synthetic polymers [60], dendrimers [61], and antibodies [62], in order to enhance the delivery of the active substance to the diseased tissue and to reduce the toxicity to healthy tissue. The use of macromolecular delivery systems provides several advantages extension of the half-life of the dmg, the ability to introduce targeting moieties into the carrier, the possibility of triggered dmg release, and the aforementioned reduced cytotoxicity. 

Numerous problems in the construction of chnically applicable drug targeting moieties still need to be solved. Of these issues, immunogenicity after repeated administration, counterproductive hver clearance, and production 5delds are the most important. Although the problem of immunogenicity is beheved to have been solved for monoclonal antibody therapy by the development of humanized and fully human antibodies [110], for other carrier systems such as modified plasma proteins and peptide modified polymers, this remains an important issue. 

Bacterial and plant toxins toxin fragments Toxic after entry into target cell fragments produced by recombinant technology have been used as targeting moiety and as effector moiety... 

Type of construct Targeting moiety Effector moiety Examples References... 

A variant of the original immunotoxin approach is the so-called immunocytokines. In these constructs the antibody targeting moiety is maintained, but the toxin as the effector molecule is replaced by a cytokine. In contrast to toxins, cytokines are often proteins endogenously produced in man. If both the antibody and cytokine are of human origin, then no foreign proteins are introduced which could provoke an antibody response from the host immune system when the drug targeting preparation is clinically applied. 

In contrast to isolated hepatocytes, liver slices retain the cellular architecture of the Uver without prior digestion with collagenase. This makes a systematic comparison of the data relating to transport of free drugs as well as drug targeting moieties from isolated hepatocytes and liver slices, an attractive model for studying the potential and limitations of the liver slice model in this area of research. 

Fig. 6 Enzymatic splitting of the oxidised polymer backbone proceeds by two different enzymes depending on the target moiety in the oxidised polymer backbone. Above, the [1-OH-ketone can be opened by an aldolase activity (apoenzyme of PVADH). Below, the diketone element is cleaved by a specific [l-diketone hydrolase (BDH). A non-enzymatic mechanism is also possible...

Fig. 2. A schematic design of a targetable polymeric conjugate. Drug and targeting moiety are bound to the soluble polymeric carrier via a spacer...

Polymeric Carrier Drug Type of Bond Targeting Moiety Type of Bond Activity in vitro Activity in vivo Ref. 

The binding methods used depend on the structure of the targeting moiety. Carbohydrates, hormones, and antibodies (or their fragments) are frequently used to direct polymer conjugates to specific cell subsets. 

Fig. 10b. A scheme of its synthesis. First, a reactive comonomer. Af-methacryloylglycyl-phenylalanylleucylgycine p-nitrophenyl ester was synthesized. In the second step a polymeric precursor is prepared by copolymerization of the reactive comonomer with A-(2-hydroxyp-ropyl)methacrylamide. After purification and characterization of the polymeric precursor, the anticancer drug (adriamycin) and targeting moiety (galactosamine) are attached by consecutive aminolysis. For details see, e.g., [169]...

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