Drug Targeting: Strategies, Principles, and Applications

ISBN-13: 9780896035317 / Angielski / Twarda / 2000 / 318 str.

G. E. Francis; Cristina Delgado; Christina Delgado

Opis

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."

Spis treści

Part I. Strategies. Chemical Construction of Immunotoxins, Victor Ghetie and Ellen S. Vitetta. Construction of Ribonuclease-Antibody Conjugates for Selective Cytotoxicity, Dianne L. Newton and Susanna M. Rybak. Intracellular Targeting Using Bispecific Antibodies, Vic Raso. Antibody Conjugation Methods for Active Targeting of Liposomes, Steven M. Ansell, Troy O. Harasym, Paul G. Tardi, Susan S. Buchkowsky, Marcel B. Bally, and Pieter R. Cullis. Folate as a Targeting Device for Proteins Utilizing Folate Receptor-Mediated Endocytosis, Robert J. Lee and Philip S. Low. Preparation of Recombinant RNase Single-Chain Antibody Fusion Proteins, Dianne L. Newton and Susanna M. Rybak. Part II. Theoretical Aspects. Practical Considerations in the Exploitation of Passive Tumor Targeting, Gillian D. Thomas. Effect of Dose, Molecular Size, and Binding Affinity on Uptake of Antibodies, Gillian D. Thomas. Inhibition of Tumor Blood Flow, Lai-Ming Ching, William R. Wilson, and Bruce C. Baguley. Part III. Applications. Targeting in Myocardial Infarction, Ban An Khaw and Vladimir P. Torchilin. Targeting HIV-Infected Cells, Seth H. Pincus. Making Fusion Toxins to Target Leukemia and Lymphoma, Robert J. Kreitman and Ira Pastan. Antibody-Bearing Liposomes as Chloroquine Vehicles in Treatment of Murine Malaria, Ajay K. Agrawal and Chhitar M. Gupta. Immunotargeting of Catalase to the Pulmonary Vascular Endothelium, Vladimir R. Muzykantov. Targeted Gene Transfer: A Practical Guide Based on Experience with Lipid-Based Plasmid Delivery Systems, Ellen K. Wasan, Dorothy L. Reimer, Pierrot Harvie, Spencer Kong, Frances M. P. Wong, and Marcel B. Bally. Index.

Blurb

In Drug Targeting: Strategies, Methods, and Protocls, Gillian E. Francis and Cristina Delgado have assembled an outstanding collection of leading-edge protocols for drug targeting studies. In addition to providing detailed step-by-step instructions, the highly experienced authors review the principal current targeting strategies, discuss how to build the constructs, examine theoretical considerations relevant to solid tumors, and describe experimental and clinical applications of targeted drug delivery systems. Also presented are new chemical and biological approaches to the preparation of targeted biopharmaceuticals, including ribonuclease-antibody chimeras, bispecific antibodies, enzyme-antibody conjugates, and folate-bearing conjugates. Applications include the targeting of myocardial infarctions using liposomal systems, the use of monoclonal antibodies to target malaria and HIV-infected cells, the targeting of fusion proteins to leukemias and lymphomas, the use of antioxidant enzyme-antibody conjugates to target the pulmonary endothelium, as well as methods addressing both the active and passive targeting of tumors.
Comprehensive and innovative, Drug Targeting: Strategies, Methods, and Protocols documents in practical detail the major new chemical and biological targeting methods now being used to produce today's emerging rich array of novel diagnostic agents and promising biopharmaceuticals.