Drug Targeting

Advances in understanding the molecular mechanisms of disease together with the advent of recombinant DNA and other technologies have opened opportunities for a vast array of novel therapeutic biopharmaceuticals and diagnostic agents. However, even natural biomolecules present a myriad of problems that limit their potential as pharmaceutical agents. Rapid degra- tion and elimination, immunological reactions, and toxicity are often asso- ated with new biopharmaceuticals, much as with conventional agents. Targeted delivery systems have the potential to increase the efficacy of existing diagnostic and therapeutic agents and also create an opportunity for the use of new pharmaceuticals, substances that themselves can be harmful to normal tissues. Both passive and active targeting have been exploited. Most active targ- ing strategies have focused on antibody conjugates since preparation of highly specific monoclonal antibodies is well established. However, a new wave of c- jugates exploiting other ligands is underway. Access to the target tissue remains an obstacle and is an area where passive targeting can be useful. In Drug Targeting: Strategies, Principles, and Applications we have tried to compile a state-of-the-art volume on current targeting approaches. The first section focuses on certain key strategies applied to date, and how to build the antibody ligand constructs. This is followed by a section on theoretical considerations for t- geting, focusing on approaches relevant to solid tumors. The last section deals with some experimental and clinical applications of targeted drug delivery systems.

Includes supplementary material: sn.pub/extras

Inhalt
Strategies.- Chemical Construction of Immunotoxins.- Construction of RibonucleaseAntibody Conjugates for Selective Cytotoxicity.- Intracellular Targeting Using Bispecific Antibodies.- Antibody Conjugation Methods for Active Targeting of Liposomes.- Folate as a Targeting Device for Proteins Utilizing Folate Receptor-Mediated Endocytosis.- Preparation of Recombinant RNase Single-Chain Antibody Fusion Proteins.- Theoretical Aspects.- Practical Considerations in the Exploitation of Passive Tumor Targeting.- Effect of Dose, Molecular Size, and Binding Affinity on Uptake of Antibodies.- Inhibition of Tumor Blood Flow.- Applications.- 10 Targeting in Myocardial Infarction.- 11 Targeting HIV-Infected Cells.- 12 Making Fusion Toxins to Target Leukemia and Lymphoma.- Antibody-Bearing Liposomes as Chloroquine Vehicles in Treatment of Murine Malaria.- 14 Immunotargeting of Catalase to the Pulmonary Vascular Endothelium.- 15 Targeted Gene Transfer.