Antibody Mediated Drug Delivery Systems: Concepts, Technology, and Applications

Yashwant Pathak , PhD, is the Associate Dean for Faculty Affairs at the College of Pharmacy, University of South Florida, Tampa, Florida. Dr. Pathak studied pharmaceutical technology at Nagpur University, India, and conflict management at Sullivan University, Kentucky. With extensive experience in academia as well as industry, he has more than 100 publications, abstracts, and reviews, two patents, five books on nanotechnology, and two books on nutraceuticals to his credit. His areas of research include drug delivery systems and their characterization in animal models. Simon Benita , PhD, is Head of the School of Pharmacy, Director of the Institute for Drug Research, and Professor of the Faculty of Medicine at The Hebrew University of Jerusalem. He holds twenty-two patents and has written 143 journal papers and seventeen book chapters. Dr. Benita has also edited three other books.

CONTRIBUTORS xv PREFACE xix CHAPTER 1 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEMS: GENERAL REVIEW AND APPLICATIONS Navdeep Kaur, Karthikeyan Subramani, and Yashwant Pathak 1 1 Historical Perspective 1 2 Antibodies 2 3 Antibody Mediation 3 4 Antibody-Mediated Drug Delivery Systems 4 5 Applications 6 6 Recent Trends 9 7 Future Trends 10 CHAPTER 2 IMMUNOLIPOSOMES FOR CARDIOVASCULAR TARGETING Tatyana Levchenko, William Hartner, and Vladimir P. Torchilin 13 1 Introduction 13 2 Immunoliposome Targeting to Pathological Regions of the Vessel Wall 14 3 Liposome Internalization by Endothelial Cells 15 4 Targeting of Atherosclerotic Lesions for Tomographic Imaging 17 5 Antibody-Mediated Liposomes for Diagnosis of Thrombosis 17 6 Thrombolytic Therapy with Immunoliposomes 18 7 Targeted Sealing of Cell Membrane Lesions: Preservation of Cell Viability 19 8 Accumulation of Liposomes and Immunoliposomes in the Ischemic Heart 21 9 Immunoliposomes as a Drug and Gene Delivery Vehicle to the Infarcted Heart 26 CHAPTER 3 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEMS FOR BREAST CANCER THERAPEUTICS Leonor Munoz Alcivar and Yashwant Pathak 35 1 Introduction 35 2 Breast Cancer 35 3 Drug Delivery Systems 36 4 Monoclonal Antibodies 37 5 Human Epidermal Growth Factor Receptor 2 40 6 Antibody-Mediated Drug Delivery System 43 7 Targets for the Treatment of Breast Cancer 45 8 Breast Cancer Therapies 46 9 The Future of Breast Cancer Therapeutics 49 10 Other Treatment Strategies 50 11 Nanotechnology 51 12 Conclusions 52 CHAPTER 4 DEVELOPMENT OF IMMUNONCONJUGATES FOR IN VIVO DELIVERY: CANCER DIAGNOSIS, IMAGING, AND THERAPY Arutselvan Natarajan 57 1 Introduction 57 2 Immunoconjugates 61 3 Immunoconjugates in Cancer Therapy 62 4 Immunoconjugates for Imaging 69 5 Immunoconjugates in Diagnostic Applications 71 6 Immunoconjugates' Promising Future and Challenges 72 7 Summary 73 CHAPTER 5 MATHEMATICAL MODELS OF ANTI-TNF THERAPIES AND THEIR CORRELATION WITH TUBERCULOSIS Simeone Marino, Mohammad Fallahi-Sichani, Jennifer J. Linderman, and Denise E. Kirschner 83 1 Introduction 83 2 Tuberculosis, TNF, and Anti-TNF Drugs 84 3 Theoretical Models To Study TB Infection 88 4 Present and Future Work 96 CHAPTER 6 TARGETED NANOPARTICLES IN RADIOTHERAPY Misty Muscarella and Yashwant Pathak 105 1 Introduction 105 2 Nanoparticles 106 3 Radiotherapy 110 4 Nanoparticles in Radiotherapy 111 5 Current and Future Developments with Nanotechnology in Radiotherapy 123 6 Conclusions 124 CHAPTER 7 ELECTRICALLY-ENHANCED DELIVERY OF DRUGS AND CONJUGATES FOR CANCER TREATMENT Arutselvan Natarajan, Luca Campana, and Raji Sundararajan 129 1 Introduction 129 2 Electroporation Mechanisms to Permeabilize the Drugs and DNAs in Cells 130 3 Electroporation-Aided Drug Delivery for Preclinical Studies 133 4 EP applications for Human Patient Studies 136 5 Future Perspectives 138 6 Summary 139 CHAPTER 8 CHARACTERIZATION OF MONOCLONAL ANTIBODY VARIANTS AND GLYCOSYLATION Ting Zheng, Srinivasa Rao, Jeff Rohrer, and Chris Pohl 145 1 Characterization of Monoclonal Antibody Heterogeneity by HPLC Analysis 145 2 Analysis of Monoclonal Antibody Glycosylation 150 CHAPTER 9 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEM FOR LYMPHATIC TARGETING TREATMENT Fang Wu, Hong Ding, and Zhirong Zhang 169 1 Introduction 169 2 Lymphatic Disorders and Their Normal Treatment 170 3 Antibody-Mediated Drug Delivery Systems for Lymphatic Targeting Treatment 172 4 Conclusions and Future Perspectives 183 CHAPTER 10 METHODS FOR NANOPARTICLE CONJUGATION TO MONOCLONAL ANTIBODIES Junling Li and Chin K. Ng 191 1 Introduction 191 2 Current Nanoparticle Systems used for Conjugation with mAbs 191 3 Conjugation Methods 192 4 Conclusions 202 CHAPTER 11 SINGLE-USE SYSTEMS IN ANIMAL CELL--BASED BIOPRODUCTION William G. Whitford 209 1 Introduction 209 2 Component Offerings 214 3 Characteristics of Single-Use Systems and Their Applications 218 CHAPTER 12 IMMUNOLIPOSOMES FOR SPECIFIC DRUG DELIVERY Manuela Calin 229 1 Introduction: Advances in Liposome Formulation 229 2 Design of Immunoliposomes for Site-Specific Drug Delivery 230 3 Cellular-Specific Targeting of Immunoliposomes 242 4 Cellular-Specific Internalization of Immunoliposomes 246 5 Immunoliposomes in Diagnosis and Therapy 247 6 Clinical Use of Immunoliposomes 251 7 Conclusions and Perspectives 252 CHAPTER 13 GENE THERAPY TARGETING KIDNEY DISEASES: ROUTES AND VEHICLES Yoshitaka Isaka, Yoshitsugu Takabatake, and Hiromi Rakugi 267 1 Introduction 267 2 Rationale for Successful Gene Targeting 268 3 Site-Specific Gene Delivery 268 4 Nuclear Import of Gene Material 270 5 Targeting the Glomerulus 270 6 Targeting the Tubule 272 7 Targeting the Interstitium 274 8 Targeting Muscle 274 9 Conclusions 275 CHAPTER 14 DETECTION OF ANTIBODIES TO POLY(ETHYLENE GLYCOL) POLYMERS USING DOUBLE-ANTIGEN-BRIDGING IMMUNOGENICITY ELISA Yijuan Liu, Helen Reidler, Jing Pan, David Milunic, Dujie Qin, Dave Chen, Yli Remo Vallejo, and Ray Yin 279 1 Introduction 279 2 Methods 280 3 Results 283 4 Discussion 286 CHAPTER 15 ANTIBODIES IN NANOMEDICINE AND MICROIMAGING METHODS Rakesh Sharma 291 1 Introduction: Antibody Molecules and Nanoparticles 291 2 Antibody-Based Nanoparticles in Microimaging 292 3 Troponin T: Newer Magnetic Immunoassay Method 317 4 Gold Nanoparticles as an Antigen Carrier and Adjuvant 330 5 Immunochemical Biosensors, Nanomedicine, and Disease 339 6 Future Directions and Conclusions 341 CHAPTER 16 METHODS FOR POLYMERIC NANOPARTICLE CONJUGATION TO MONOCLONAL ANTIBODIES Uyen Minh Le, Hieu Tran, and Yashwant Pathak 351 1 Introduction 351 2 Conjugation of mAb and Polyethylenimine Nanoparticles 353 3 Conjugation of mAb to Poly(Lactide-CO-Glycolide) Nanoparticles 357 4 Conjugation of mAb to Poly(Lactic Acid) and its Derivatives 359 5 Conjugation of mAb to Other Polymeric Nanoparticles 360 6 Summary 361 CHAPTER 17 PLANT-DERIVED ANTIBODIES FOR ACADEMIC, INDUSTRIAL, AND THERAPEUTIC APPLICATIONS Slavko Komarnytsky and Nikolai Borisjuk 365 1 Historical Perspective 365 2 Plant-Based Production of Recombinant Proteins 366 3 Expression in an Entire Plant Versus a Plant Organ 367 4 ER Targeting and Secretion of Recombinant Proteins 368 5 Expression in Seeds 370 6 Transient Expression 371 7 Glycosylation 373 8 Recent Examples of Plant-Derived Antibodies Effective in Mammalian Systems 375 9 Conclusions 376 CHAPTER 18 MONOCLONAL ANTIBODIES AS BIOPHARMACEUTICALS Girish J. Kotwal 383 1 Historical Perspective 383 2 Introduction 384 3 Structure and Types of mAbs 385 4 Mechanism of Action 385 5 FDA-approved mAb Biopharmaceuticals in Current Use 386 6 Future of Monoclonal Antibodies as Biopharmaceuticals 389 CHAPTER 19 PULMONARY TARGETING OF NANOPARTICLES AND MONOCLONAL ANTIBODIES Weiyuan Chang 391 1 Introduction 391 2 Attributes of mAbs as Therapeutics for Pulmonary Diseases 392 3 Antibody-Conjugated Nanoparticles for Lung Targeting 393 4 Monoclonal Antibodies in the Treatment of Asthma 394 5 Monoclonal Antibodies in the Treatment of COPD 398 6 Challenges in Pulmonary Disease 400 7 Conclusions 402 CHAPTER 20 ANTIBODY-MEDIATED ARTHRITIS AND NEW THERAPEUTIC AVENUES Kutty Selva Nandakumar 407 1 Autoantibodies in Rheumatoid Arthritis 407 2 Role of Cartilage Antigen-Specific Antibodies in Inducing Arthritis 408 3 Arthritis Mediation Through Antibodies Recognizing Citrullinated Antigens 413 4 Regulation at the Effector Level 414 5 Cartilage Damage Independent of Inflammatory Mediators 414 6 pathogenicity of GPI-Specific Antibodies 415 7 Therapeutic Cleavage of Arthritogenic Antibodies 415 8 Arthritis Attenuation Though Removal of Specific Sugars on IgG 417 CHAPTER 21 IMMUNONANOPARTICLES FOR NUCLEAR IMAGING AND RADIOTHERAPY Oren Giladi and Simon Benita 427 1 Radioisotopes and Radiopharmaceuticals 427 2 Radiolabeled Antibodies 432 3 Radiolabeled Nanoparticles 437 4 Future Perspectives and Conclusions 449 CHAPTER 22 MONOCLONAL ANTIBODIES IN THE TREATMENT OF ASTHMA Glenn J. Whelan 457 1 Introduction 457 2 IgE 458 3 TNFalpha 460 4 IL-5 462 5 IL-9 464 6 IL-4 and IL-13 465 7 Targeting the T-cell 467 8 Conclusions 468 References 469 INDEX 473