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

A comprehensive guide to the concepts, technology, and applications of antibody–mediated drug delivery systems

Antibody–Mediated Drug Delivery Systems: Concepts, Technology, and Applications provides readers with comprehensive coverage of one of the fastest growing fields of pharmaceutical and biotechnology research. An up–to–date, practical reference on the essential ideas, analytical developments, processing, and utilization of antibody–mediated drug delivery systems, this edited volume features contributions from acclaimed experts from around the globe.

Each of the twenty–two chapters explores the opportunities, challenges, and uses of antibody–mediated delivery systems for generating novel therapeutic treatments. Topics covered include targeted treatments for cancer, cardiovascular diseases, asthma, and other conditions, as well as brain drug delivery, vaccine delivery, plant–derived antibodies, gene therapy, and more.

Six of the ten bestselling drugs on the market today are therapeutic antibodies, yet no definitive and detailed review of current developments in the field has been published since 1988. Antibody–Mediated Drug Delivery Systems fills this hole in the literature, with insightful coverage of the full spectrum of essential concepts, technologies, and applications of these treatments, making it an essential resource for medical and scientific researchers and students working in industry and academia.

CONTRIBUTORS xv

PREFACE xix

CHAPTER 1 ANTIBODY–MEDIATED DRUG DELIVERY SYSTEMS: GENERALREVIEW AND APPLICATIONS
Navdeep Kaur, Karthikeyan Subramani, and Yashwant Pathak1

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 CARDIOVASCULARTARGETING
Tatyana Levchenko, William Hartner, and Vladimir P. Torchilin13

1 Introduction 13

2 Immunoliposome Targeting to Pathological Regions of the VesselWall 14

3 Liposome Internalization by Endothelial Cells 15

4 Targeting of Atherosclerotic Lesions for Tomographic Imaging17

5 Antibody–Mediated Liposomes for Diagnosis of Thrombosis 17

6 Thrombolytic Therapy with Immunoliposomes 18

7 Targeted Sealing of Cell Membrane Lesions: Preservation ofCell Viability 19

8 Accumulation of Liposomes and Immunoliposomes in the IschemicHeart 21

9 Immunoliposomes as a Drug and Gene Delivery Vehicle to theInfarcted Heart 26

CHAPTER 3 ANTIBODY–MEDIATED DRUG DELIVERY SYSTEMS FOR BREASTCANCER 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 VIVODELIVERY: 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 THEIRCORRELATION 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 inRadiotherapy 123

6 Conclusions 124

CHAPTER 7 ELECTRICALLY–ENHANCED DELIVERY OF DRUGS ANDCONJUGATES FOR CANCER TREATMENT
Arutselvan Natarajan, Luca Campana, and Raji Sundararajan129

1 Introduction 129

2 Electroporation Mechanisms to Permeabilize the Drugs and DNAsin Cells 130

3 Electroporation–Aided Drug Delivery for Preclinical Studies133

4 EP applications for Human Patient Studies 136

5 Future Perspectives 138

6 Summary 139

CHAPTER 8 CHARACTERIZATION OF MONOCLONAL ANTIBODY VARIANTSAND GLYCOSYLATION
Ting Zheng, Srinivasa Rao, Jeff Rohrer, and Chris Pohl145

1 Characterization of Monoclonal Antibody Heterogeneity by HPLCAnalysis 145

2 Analysis of Monoclonal Antibody Glycosylation 150

CHAPTER 9 ANTIBODY–MEDIATED DRUG DELIVERY SYSTEM FORLYMPHATIC 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 LymphaticTargeting Treatment 172

4 Conclusions and Future Perspectives 183

CHAPTER 10 METHODS FOR NANOPARTICLE CONJUGATION TO MONOCLONALANTIBODIES
Junling Li and Chin K. Ng 191

1 Introduction 191

2 Current Nanoparticle Systems used for Conjugation with mAbs191

3 Conjugation Methods 192

4 Conclusions 202

CHAPTER 11 SINGLE–USE SYSTEMS IN ANIMAL CELL BASEDBIOPRODUCTION
William G. Whitford 209

1 Introduction 209

2 Component Offerings 214

3 Characteristics of Single–Use Systems and Their Applications218

CHAPTER 12 IMMUNOLIPOSOMES FOR SPECIFIC DRUGDELIVERY
Manuela Calin 229

1 Introduction: Advances in Liposome Formulation 229

2 Design of Immunoliposomes for Site–Specific Drug Delivery230

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 ANDVEHICLES
Yoshitaka Isaka, Yoshitsugu Takabatake, and Hiromi Rakugi267

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 IMMUNOGENICITYELISA
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 MICROIMAGINGMETHODS
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 TOMONOCLONAL 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) Nanoparticles357

4 Conjugation of mAb to Poly(Lactic Acid) and its Derivatives359

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 inMammalian Systems 375

9 Conclusions 376

CHAPTER 18 MONOCLONAL ANTIBODIES ASBIOPHARMACEUTICALS
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 ANDMONOCLONAL ANTIBODIES
Weiyuan Chang 391

1 Introduction 391

2 Attributes of mAbs as Therapeutics for Pulmonary Diseases392

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 THERAPEUTICAVENUES
Kutty Selva Nandakumar 407

1 Autoantibodies in Rheumatoid Arthritis 407

2 Role of Cartilage Antigen–Specific Antibodies in InducingArthritis 408

3 Arthritis Mediation Through Antibodies RecognizingCitrullinated 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 IgG417

CHAPTER 21 IMMUNONANOPARTICLES FOR NUCLEAR IMAGING ANDRADIOTHERAPY
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 OFASTHMA
Glenn J. Whelan 457

1 Introduction 457

2 IgE 458

3 TNF 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

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.