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 xvPREFACE xixCHAPTER 1 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEMS: GENERAL REVIEW AND APPLICATIONSNavdeep Kaur, Karthikeyan Subramani, and Yashwant Pathak 11 Historical Perspective 12 Antibodies 23 Antibody Mediation 34 Antibody-Mediated Drug Delivery Systems 45 Applications 66 Recent Trends 97 Future Trends 10CHAPTER 2 IMMUNOLIPOSOMES FOR CARDIOVASCULAR TARGETINGTatyana Levchenko, William Hartner, and Vladimir P. Torchilin 131 Introduction 132 Immunoliposome Targeting to Pathological Regions of the Vessel Wall 143 Liposome Internalization by Endothelial Cells 154 Targeting of Atherosclerotic Lesions for Tomographic Imaging 175 Antibody-Mediated Liposomes for Diagnosis of Thrombosis 176 Thrombolytic Therapy with Immunoliposomes 187 Targeted Sealing of Cell Membrane Lesions: Preservation of Cell Viability 198 Accumulation of Liposomes and Immunoliposomes in the Ischemic Heart 219 Immunoliposomes as a Drug and Gene Delivery Vehicle to the Infarcted Heart 26CHAPTER 3 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEMS FOR BREAST CANCER THERAPEUTICSLeonor Munoz Alcivar and Yashwant Pathak 351 Introduction 352 Breast Cancer 353 Drug Delivery Systems 364 Monoclonal Antibodies 375 Human Epidermal Growth Factor Receptor 2 406 Antibody-Mediated Drug Delivery System 437 Targets for the Treatment of Breast Cancer 458 Breast Cancer Therapies 469 The Future of Breast Cancer Therapeutics 4910 Other Treatment Strategies 5011 Nanotechnology 5112 Conclusions 52CHAPTER 4 DEVELOPMENT OF IMMUNONCONJUGATES FOR IN VIVO DELIVERY: CANCER DIAGNOSIS, IMAGING, AND THERAPYArutselvan Natarajan 571 Introduction 572 Immunoconjugates 613 Immunoconjugates in Cancer Therapy 624 Immunoconjugates for Imaging 695 Immunoconjugates in Diagnostic Applications 716 Immunoconjugates’ Promising Future and Challenges 727 Summary 73CHAPTER 5 MATHEMATICAL MODELS OF ANTI-TNF THERAPIES AND THEIR CORRELATION WITH TUBERCULOSISSimeone Marino, Mohammad Fallahi-Sichani, Jennifer J. Linderman, and Denise E. Kirschner 831 Introduction 832 Tuberculosis, TNF, and Anti-TNF Drugs 843 Theoretical Models To Study TB Infection 884 Present and Future Work 96CHAPTER 6 TARGETED NANOPARTICLES IN RADIOTHERAPYMisty Muscarella and Yashwant Pathak 1051 Introduction 1052 Nanoparticles 1063 Radiotherapy 1104 Nanoparticles in Radiotherapy 1115 Current and Future Developments with Nanotechnology in Radiotherapy 1236 Conclusions 124CHAPTER 7 ELECTRICALLY-ENHANCED DELIVERY OF DRUGS AND CONJUGATES FOR CANCER TREATMENTArutselvan Natarajan, Luca Campana, and Raji Sundararajan 1291 Introduction 1292 Electroporation Mechanisms to Permeabilize the Drugs and DNAs in Cells 1303 Electroporation-Aided Drug Delivery for Preclinical Studies 1334 EP applications for Human Patient Studies 1365 Future Perspectives 1386 Summary 139CHAPTER 8 CHARACTERIZATION OF MONOCLONAL ANTIBODY VARIANTS AND GLYCOSYLATIONTing Zheng, Srinivasa Rao, Jeff Rohrer, and Chris Pohl 1451 Characterization of Monoclonal Antibody Heterogeneity by HPLC Analysis 1452 Analysis of Monoclonal Antibody Glycosylation 150CHAPTER 9 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEM FOR LYMPHATIC TARGETING TREATMENTFang Wu, Hong Ding, and Zhirong Zhang 1691 Introduction 1692 Lymphatic Disorders and Their Normal Treatment 1703 Antibody-Mediated Drug Delivery Systems for Lymphatic Targeting Treatment 1724 Conclusions and Future Perspectives 183CHAPTER 10 METHODS FOR NANOPARTICLE CONJUGATION TO MONOCLONAL ANTIBODIESJunling Li and Chin K. Ng 1911 Introduction 1912 Current Nanoparticle Systems used for Conjugation with mAbs 1913 Conjugation Methods 1924 Conclusions 202CHAPTER 11 SINGLE-USE SYSTEMS IN ANIMAL CELL–BASED BIOPRODUCTIONWilliam G. Whitford 2091 Introduction 2092 Component Offerings 2143 Characteristics of Single-Use Systems and Their Applications 218CHAPTER 12 IMMUNOLIPOSOMES FOR SPECIFIC DRUG DELIVERYManuela Calin 2291 Introduction: Advances in Liposome Formulation 2292 Design of Immunoliposomes for Site-Specific Drug Delivery 2303 Cellular-Specific Targeting of Immunoliposomes 2424 Cellular-Specific Internalization of Immunoliposomes 2465 Immunoliposomes in Diagnosis and Therapy 2476 Clinical Use of Immunoliposomes 2517 Conclusions and Perspectives 252CHAPTER 13 GENE THERAPY TARGETING KIDNEY DISEASES: ROUTES AND VEHICLESYoshitaka Isaka, Yoshitsugu Takabatake, and Hiromi Rakugi 2671 Introduction 2672 Rationale for Successful Gene Targeting 2683 Site-Specific Gene Delivery 2684 Nuclear Import of Gene Material 2705 Targeting the Glomerulus 2706 Targeting the Tubule 2727 Targeting the Interstitium 2748 Targeting Muscle 2749 Conclusions 275CHAPTER 14 DETECTION OF ANTIBODIES TO POLY(ETHYLENE GLYCOL) POLYMERS USING DOUBLE-ANTIGEN-BRIDGING IMMUNOGENICITY ELISAYijuan Liu, Helen Reidler, Jing Pan, David Milunic, Dujie Qin, Dave Chen, Yli Remo Vallejo, and Ray Yin 2791 Introduction 2792 Methods 2803 Results 2834 Discussion 286CHAPTER 15 ANTIBODIES IN NANOMEDICINE AND MICROIMAGING METHODSRakesh Sharma 2911 Introduction: Antibody Molecules and Nanoparticles 2912 Antibody-Based Nanoparticles in Microimaging 2923 Troponin T: Newer Magnetic Immunoassay Method 3174 Gold Nanoparticles as an Antigen Carrier and Adjuvant 3305 Immunochemical Biosensors, Nanomedicine, and Disease 3396 Future Directions and Conclusions 341CHAPTER 16 METHODS FOR POLYMERIC NANOPARTICLE CONJUGATION TO MONOCLONAL ANTIBODIESUyen Minh Le, Hieu Tran, and Yashwant Pathak 3511 Introduction 3512 Conjugation of mAb and Polyethylenimine Nanoparticles 3533 Conjugation of mAb to Poly(Lactide-CO-Glycolide) Nanoparticles 3574 Conjugation of mAb to Poly(Lactic Acid) and its Derivatives 3595 Conjugation of mAb to Other Polymeric Nanoparticles 3606 Summary 361CHAPTER 17 PLANT-DERIVED ANTIBODIES FOR ACADEMIC, INDUSTRIAL, AND THERAPEUTIC APPLICATIONSSlavko Komarnytsky and Nikolai Borisjuk 3651 Historical Perspective 3652 Plant-Based Production of Recombinant Proteins 3663 Expression in an Entire Plant Versus a Plant Organ 3674 ER Targeting and Secretion of Recombinant Proteins 3685 Expression in Seeds 3706 Transient Expression 3717 Glycosylation 3738 Recent Examples of Plant-Derived Antibodies Effective in Mammalian Systems 3759 Conclusions 376CHAPTER 18 MONOCLONAL ANTIBODIES AS BIOPHARMACEUTICALSGirish J. Kotwal 3831 Historical Perspective 3832 Introduction 3843 Structure and Types of mAbs 3854 Mechanism of Action 3855 FDA-approved mAb Biopharmaceuticals in Current Use 3866 Future of Monoclonal Antibodies as Biopharmaceuticals 389CHAPTER 19 PULMONARY TARGETING OF NANOPARTICLES AND MONOCLONAL ANTIBODIESWeiyuan Chang 3911 Introduction 3912 Attributes of mAbs as Therapeutics for Pulmonary Diseases 3923 Antibody-Conjugated Nanoparticles for Lung Targeting 3934 Monoclonal Antibodies in the Treatment of Asthma 3945 Monoclonal Antibodies in the Treatment of COPD 3986 Challenges in Pulmonary Disease 4007 Conclusions 402CHAPTER 20 ANTIBODY-MEDIATED ARTHRITIS AND NEW THERAPEUTIC AVENUESKutty Selva Nandakumar 4071 Autoantibodies in Rheumatoid Arthritis 4072 Role of Cartilage Antigen-Specific Antibodies in Inducing Arthritis 4083 Arthritis Mediation Through Antibodies Recognizing Citrullinated Antigens 4134 Regulation at the Effector Level 4145 Cartilage Damage Independent of Inflammatory Mediators 4146 pathogenicity of GPI-Specific Antibodies 4157 Therapeutic Cleavage of Arthritogenic Antibodies 4158 Arthritis Attenuation Though Removal of Specific Sugars on IgG 417CHAPTER 21 IMMUNONANOPARTICLES FOR NUCLEAR IMAGING AND RADIOTHERAPYOren Giladi and Simon Benita 4271 Radioisotopes and Radiopharmaceuticals 4272 Radiolabeled Antibodies 4323 Radiolabeled Nanoparticles 4374 Future Perspectives and Conclusions 449CHAPTER 22 MONOCLONAL ANTIBODIES IN THE TREATMENT OF ASTHMAGlenn J. Whelan 4571 Introduction 4572 IgE 4583 TNFα 4604 IL-5 4625 IL-9 4646 IL-4 and IL-13 4657 Targeting the T-cell 4678 Conclusions 468References 469INDEX 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.

• CONTRIBUTORS xvPREFACE xixCHAPTER 1 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEMS: GENERAL REVIEW AND APPLICATIONSNavdeep Kaur, Karthikeyan Subramani, and Yashwant Pathak 11 Historical Perspective 12 Antibodies 23 Antibody Mediation 34 Antibody-Mediated Drug Delivery Systems 45 Applications 66 Recent Trends 97 Future Trends 10CHAPTER 2 IMMUNOLIPOSOMES FOR CARDIOVASCULAR TARGETINGTatyana Levchenko, William Hartner, and Vladimir P. Torchilin 131 Introduction 132 Immunoliposome Targeting to Pathological Regions of the Vessel Wall 143 Liposome Internalization by Endothelial Cells 154 Targeting of Atherosclerotic Lesions for Tomographic Imaging 175 Antibody-Mediated Liposomes for Diagnosis of Thrombosis 176 Thrombolytic Therapy with Immunoliposomes 187 Targeted Sealing of Cell Membrane Lesions: Preservation of Cell Viability 198 Accumulation of Liposomes and Immunoliposomes in the Ischemic Heart 219 Immunoliposomes as a Drug and Gene Delivery Vehicle to the Infarcted Heart 26CHAPTER 3 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEMS FOR BREAST CANCER THERAPEUTICSLeonor Munoz Alcivar and Yashwant Pathak 351 Introduction 352 Breast Cancer 353 Drug Delivery Systems 364 Monoclonal Antibodies 375 Human Epidermal Growth Factor Receptor 2 406 Antibody-Mediated Drug Delivery System 437 Targets for the Treatment of Breast Cancer 458 Breast Cancer Therapies 469 The Future of Breast Cancer Therapeutics 4910 Other Treatment Strategies 5011 Nanotechnology 5112 Conclusions 52CHAPTER 4 DEVELOPMENT OF IMMUNONCONJUGATES FOR IN VIVO DELIVERY: CANCER DIAGNOSIS, IMAGING, AND THERAPYArutselvan Natarajan 571 Introduction 572 Immunoconjugates 613 Immunoconjugates in Cancer Therapy 624 Immunoconjugates for Imaging 695 Immunoconjugates in Diagnostic Applications 716 Immunoconjugates’ Promising Future and Challenges 727 Summary 73CHAPTER 5 MATHEMATICAL MODELS OF ANTI-TNF THERAPIES AND THEIR CORRELATION WITH TUBERCULOSISSimeone Marino, Mohammad Fallahi-Sichani, Jennifer J. Linderman, and Denise E. Kirschner 831 Introduction 832 Tuberculosis, TNF, and Anti-TNF Drugs 843 Theoretical Models To Study TB Infection 884 Present and Future Work 96CHAPTER 6 TARGETED NANOPARTICLES IN RADIOTHERAPYMisty Muscarella and Yashwant Pathak 1051 Introduction 1052 Nanoparticles 1063 Radiotherapy 1104 Nanoparticles in Radiotherapy 1115 Current and Future Developments with Nanotechnology in Radiotherapy 1236 Conclusions 124CHAPTER 7 ELECTRICALLY-ENHANCED DELIVERY OF DRUGS AND CONJUGATES FOR CANCER TREATMENTArutselvan Natarajan, Luca Campana, and Raji Sundararajan 1291 Introduction 1292 Electroporation Mechanisms to Permeabilize the Drugs and DNAs in Cells 1303 Electroporation-Aided Drug Delivery for Preclinical Studies 1334 EP applications for Human Patient Studies 1365 Future Perspectives 1386 Summary 139CHAPTER 8 CHARACTERIZATION OF MONOCLONAL ANTIBODY VARIANTS AND GLYCOSYLATIONTing Zheng, Srinivasa Rao, Jeff Rohrer, and Chris Pohl 1451 Characterization of Monoclonal Antibody Heterogeneity by HPLC Analysis 1452 Analysis of Monoclonal Antibody Glycosylation 150CHAPTER 9 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEM FOR LYMPHATIC TARGETING TREATMENTFang Wu, Hong Ding, and Zhirong Zhang 1691 Introduction 1692 Lymphatic Disorders and Their Normal Treatment 1703 Antibody-Mediated Drug Delivery Systems for Lymphatic Targeting Treatment 1724 Conclusions and Future Perspectives 183CHAPTER 10 METHODS FOR NANOPARTICLE CONJUGATION TO MONOCLONAL ANTIBODIESJunling Li and Chin K. Ng 1911 Introduction 1912 Current Nanoparticle Systems used for Conjugation with mAbs 1913 Conjugation Methods 1924 Conclusions 202CHAPTER 11 SINGLE-USE SYSTEMS IN ANIMAL CELL–BASED BIOPRODUCTIONWilliam G. Whitford 2091 Introduction 2092 Component Offerings 2143 Characteristics of Single-Use Systems and Their Applications 218CHAPTER 12 IMMUNOLIPOSOMES FOR SPECIFIC DRUG DELIVERYManuela Calin 2291 Introduction: Advances in Liposome Formulation 2292 Design of Immunoliposomes for Site-Specific Drug Delivery 2303 Cellular-Specific Targeting of Immunoliposomes 2424 Cellular-Specific Internalization of Immunoliposomes 2465 Immunoliposomes in Diagnosis and Therapy 2476 Clinical Use of Immunoliposomes 2517 Conclusions and Perspectives 252CHAPTER 13 GENE THERAPY TARGETING KIDNEY DISEASES: ROUTES AND VEHICLESYoshitaka Isaka, Yoshitsugu Takabatake, and Hiromi Rakugi 2671 Introduction 2672 Rationale for Successful Gene Targeting 2683 Site-Specific Gene Delivery 2684 Nuclear Import of Gene Material 2705 Targeting the Glomerulus 2706 Targeting the Tubule 2727 Targeting the Interstitium 2748 Targeting Muscle 2749 Conclusions 275CHAPTER 14 DETECTION OF ANTIBODIES TO POLY(ETHYLENE GLYCOL) POLYMERS USING DOUBLE-ANTIGEN-BRIDGING IMMUNOGENICITY ELISAYijuan Liu, Helen Reidler, Jing Pan, David Milunic, Dujie Qin, Dave Chen, Yli Remo Vallejo, and Ray Yin 2791 Introduction 2792 Methods 2803 Results 2834 Discussion 286CHAPTER 15 ANTIBODIES IN NANOMEDICINE AND MICROIMAGING METHODSRakesh Sharma 2911 Introduction: Antibody Molecules and Nanoparticles 2912 Antibody-Based Nanoparticles in Microimaging 2923 Troponin T: Newer Magnetic Immunoassay Method 3174 Gold Nanoparticles as an Antigen Carrier and Adjuvant 3305 Immunochemical Biosensors, Nanomedicine, and Disease 3396 Future Directions and Conclusions 341CHAPTER 16 METHODS FOR POLYMERIC NANOPARTICLE CONJUGATION TO MONOCLONAL ANTIBODIESUyen Minh Le, Hieu Tran, and Yashwant Pathak 3511 Introduction 3512 Conjugation of mAb and Polyethylenimine Nanoparticles 3533 Conjugation of mAb to Poly(Lactide-CO-Glycolide) Nanoparticles 3574 Conjugation of mAb to Poly(Lactic Acid) and its Derivatives 3595 Conjugation of mAb to Other Polymeric Nanoparticles 3606 Summary 361CHAPTER 17 PLANT-DERIVED ANTIBODIES FOR ACADEMIC, INDUSTRIAL, AND THERAPEUTIC APPLICATIONSSlavko Komarnytsky and Nikolai Borisjuk 3651 Historical Perspective 3652 Plant-Based Production of Recombinant Proteins 3663 Expression in an Entire Plant Versus a Plant Organ 3674 ER Targeting and Secretion of Recombinant Proteins 3685 Expression in Seeds 3706 Transient Expression 3717 Glycosylation 3738 Recent Examples of Plant-Derived Antibodies Effective in Mammalian Systems 3759 Conclusions 376CHAPTER 18 MONOCLONAL ANTIBODIES AS BIOPHARMACEUTICALSGirish J. Kotwal 3831 Historical Perspective 3832 Introduction 3843 Structure and Types of mAbs 3854 Mechanism of Action 3855 FDA-approved mAb Biopharmaceuticals in Current Use 3866 Future of Monoclonal Antibodies as Biopharmaceuticals 389CHAPTER 19 PULMONARY TARGETING OF NANOPARTICLES AND MONOCLONAL ANTIBODIESWeiyuan Chang 3911 Introduction 3912 Attributes of mAbs as Therapeutics for Pulmonary Diseases 3923 Antibody-Conjugated Nanoparticles for Lung Targeting 3934 Monoclonal Antibodies in the Treatment of Asthma 3945 Monoclonal Antibodies in the Treatment of COPD 3986 Challenges in Pulmonary Disease 4007 Conclusions 402CHAPTER 20 ANTIBODY-MEDIATED ARTHRITIS AND NEW THERAPEUTIC AVENUESKutty Selva Nandakumar 4071 Autoantibodies in Rheumatoid Arthritis 4072 Role of Cartilage Antigen-Specific Antibodies in Inducing Arthritis 4083 Arthritis Mediation Through Antibodies Recognizing Citrullinated Antigens 4134 Regulation at the Effector Level 4145 Cartilage Damage Independent of Inflammatory Mediators 4146 pathogenicity of GPI-Specific Antibodies 4157 Therapeutic Cleavage of Arthritogenic Antibodies 4158 Arthritis Attenuation Though Removal of Specific Sugars on IgG 417CHAPTER 21 IMMUNONANOPARTICLES FOR NUCLEAR IMAGING AND RADIOTHERAPYOren Giladi and Simon Benita 4271 Radioisotopes and Radiopharmaceuticals 4272 Radiolabeled Antibodies 4323 Radiolabeled Nanoparticles 4374 Future Perspectives and Conclusions 449CHAPTER 22 MONOCLONAL ANTIBODIES IN THE TREATMENT OF ASTHMAGlenn J. Whelan 4571 Introduction 4572 IgE 4583 TNFα 4604 IL-5 4625 IL-9 4646 IL-4 and IL-13 4657 Targeting the T-cell 4678 Conclusions 468References 469INDEX 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.

• CONTRIBUTORS xvPREFACE xixCHAPTER 1 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEMS: GENERAL REVIEW AND APPLICATIONSNavdeep Kaur, Karthikeyan Subramani, and Yashwant Pathak 11 Historical Perspective 12 Antibodies 23 Antibody Mediation 34 Antibody-Mediated Drug Delivery Systems 45 Applications 66 Recent Trends 97 Future Trends 10CHAPTER 2 IMMUNOLIPOSOMES FOR CARDIOVASCULAR TARGETINGTatyana Levchenko, William Hartner, and Vladimir P. Torchilin 131 Introduction 132 Immunoliposome Targeting to Pathological Regions of the Vessel Wall 143 Liposome Internalization by Endothelial Cells 154 Targeting of Atherosclerotic Lesions for Tomographic Imaging 175 Antibody-Mediated Liposomes for Diagnosis of Thrombosis 176 Thrombolytic Therapy with Immunoliposomes 187 Targeted Sealing of Cell Membrane Lesions: Preservation of Cell Viability 198 Accumulation of Liposomes and Immunoliposomes in the Ischemic Heart 219 Immunoliposomes as a Drug and Gene Delivery Vehicle to the Infarcted Heart 26CHAPTER 3 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEMS FOR BREAST CANCER THERAPEUTICSLeonor Munoz Alcivar and Yashwant Pathak 351 Introduction 352 Breast Cancer 353 Drug Delivery Systems 364 Monoclonal Antibodies 375 Human Epidermal Growth Factor Receptor 2 406 Antibody-Mediated Drug Delivery System 437 Targets for the Treatment of Breast Cancer 458 Breast Cancer Therapies 469 The Future of Breast Cancer Therapeutics 4910 Other Treatment Strategies 5011 Nanotechnology 5112 Conclusions 52CHAPTER 4 DEVELOPMENT OF IMMUNONCONJUGATES FOR IN VIVO DELIVERY: CANCER DIAGNOSIS, IMAGING, AND THERAPYArutselvan Natarajan 571 Introduction 572 Immunoconjugates 613 Immunoconjugates in Cancer Therapy 624 Immunoconjugates for Imaging 695 Immunoconjugates in Diagnostic Applications 716 Immunoconjugates’ Promising Future and Challenges 727 Summary 73CHAPTER 5 MATHEMATICAL MODELS OF ANTI-TNF THERAPIES AND THEIR CORRELATION WITH TUBERCULOSISSimeone Marino, Mohammad Fallahi-Sichani, Jennifer J. Linderman, and Denise E. Kirschner 831 Introduction 832 Tuberculosis, TNF, and Anti-TNF Drugs 843 Theoretical Models To Study TB Infection 884 Present and Future Work 96CHAPTER 6 TARGETED NANOPARTICLES IN RADIOTHERAPYMisty Muscarella and Yashwant Pathak 1051 Introduction 1052 Nanoparticles 1063 Radiotherapy 1104 Nanoparticles in Radiotherapy 1115 Current and Future Developments with Nanotechnology in Radiotherapy 1236 Conclusions 124CHAPTER 7 ELECTRICALLY-ENHANCED DELIVERY OF DRUGS AND CONJUGATES FOR CANCER TREATMENTArutselvan Natarajan, Luca Campana, and Raji Sundararajan 1291 Introduction 1292 Electroporation Mechanisms to Permeabilize the Drugs and DNAs in Cells 1303 Electroporation-Aided Drug Delivery for Preclinical Studies 1334 EP applications for Human Patient Studies 1365 Future Perspectives 1386 Summary 139CHAPTER 8 CHARACTERIZATION OF MONOCLONAL ANTIBODY VARIANTS AND GLYCOSYLATIONTing Zheng, Srinivasa Rao, Jeff Rohrer, and Chris Pohl 1451 Characterization of Monoclonal Antibody Heterogeneity by HPLC Analysis 1452 Analysis of Monoclonal Antibody Glycosylation 150CHAPTER 9 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEM FOR LYMPHATIC TARGETING TREATMENTFang Wu, Hong Ding, and Zhirong Zhang 1691 Introduction 1692 Lymphatic Disorders and Their Normal Treatment 1703 Antibody-Mediated Drug Delivery Systems for Lymphatic Targeting Treatment 1724 Conclusions and Future Perspectives 183CHAPTER 10 METHODS FOR NANOPARTICLE CONJUGATION TO MONOCLONAL ANTIBODIESJunling Li and Chin K. Ng 1911 Introduction 1912 Current Nanoparticle Systems used for Conjugation with mAbs 1913 Conjugation Methods 1924 Conclusions 202CHAPTER 11 SINGLE-USE SYSTEMS IN ANIMAL CELL–BASED BIOPRODUCTIONWilliam G. Whitford 2091 Introduction 2092 Component Offerings 2143 Characteristics of Single-Use Systems and Their Applications 218CHAPTER 12 IMMUNOLIPOSOMES FOR SPECIFIC DRUG DELIVERYManuela Calin 2291 Introduction: Advances in Liposome Formulation 2292 Design of Immunoliposomes for Site-Specific Drug Delivery 2303 Cellular-Specific Targeting of Immunoliposomes 2424 Cellular-Specific Internalization of Immunoliposomes 2465 Immunoliposomes in Diagnosis and Therapy 2476 Clinical Use of Immunoliposomes 2517 Conclusions and Perspectives 252CHAPTER 13 GENE THERAPY TARGETING KIDNEY DISEASES: ROUTES AND VEHICLESYoshitaka Isaka, Yoshitsugu Takabatake, and Hiromi Rakugi 2671 Introduction 2672 Rationale for Successful Gene Targeting 2683 Site-Specific Gene Delivery 2684 Nuclear Import of Gene Material 2705 Targeting the Glomerulus 2706 Targeting the Tubule 2727 Targeting the Interstitium 2748 Targeting Muscle 2749 Conclusions 275CHAPTER 14 DETECTION OF ANTIBODIES TO POLY(ETHYLENE GLYCOL) POLYMERS USING DOUBLE-ANTIGEN-BRIDGING IMMUNOGENICITY ELISAYijuan Liu, Helen Reidler, Jing Pan, David Milunic, Dujie Qin, Dave Chen, Yli Remo Vallejo, and Ray Yin 2791 Introduction 2792 Methods 2803 Results 2834 Discussion 286CHAPTER 15 ANTIBODIES IN NANOMEDICINE AND MICROIMAGING METHODSRakesh Sharma 2911 Introduction: Antibody Molecules and Nanoparticles 2912 Antibody-Based Nanoparticles in Microimaging 2923 Troponin T: Newer Magnetic Immunoassay Method 3174 Gold Nanoparticles as an Antigen Carrier and Adjuvant 3305 Immunochemical Biosensors, Nanomedicine, and Disease 3396 Future Directions and Conclusions 341CHAPTER 16 METHODS FOR POLYMERIC NANOPARTICLE CONJUGATION TO MONOCLONAL ANTIBODIESUyen Minh Le, Hieu Tran, and Yashwant Pathak 3511 Introduction 3512 Conjugation of mAb and Polyethylenimine Nanoparticles 3533 Conjugation of mAb to Poly(Lactide-CO-Glycolide) Nanoparticles 3574 Conjugation of mAb to Poly(Lactic Acid) and its Derivatives 3595 Conjugation of mAb to Other Polymeric Nanoparticles 3606 Summary 361CHAPTER 17 PLANT-DERIVED ANTIBODIES FOR ACADEMIC, INDUSTRIAL, AND THERAPEUTIC APPLICATIONSSlavko Komarnytsky and Nikolai Borisjuk 3651 Historical Perspective 3652 Plant-Based Production of Recombinant Proteins 3663 Expression in an Entire Plant Versus a Plant Organ 3674 ER Targeting and Secretion of Recombinant Proteins 3685 Expression in Seeds 3706 Transient Expression 3717 Glycosylation 3738 Recent Examples of Plant-Derived Antibodies Effective in Mammalian Systems 3759 Conclusions 376CHAPTER 18 MONOCLONAL ANTIBODIES AS BIOPHARMACEUTICALSGirish J. Kotwal 3831 Historical Perspective 3832 Introduction 3843 Structure and Types of mAbs 3854 Mechanism of Action 3855 FDA-approved mAb Biopharmaceuticals in Current Use 3866 Future of Monoclonal Antibodies as Biopharmaceuticals 389CHAPTER 19 PULMONARY TARGETING OF NANOPARTICLES AND MONOCLONAL ANTIBODIESWeiyuan Chang 3911 Introduction 3912 Attributes of mAbs as Therapeutics for Pulmonary Diseases 3923 Antibody-Conjugated Nanoparticles for Lung Targeting 3934 Monoclonal Antibodies in the Treatment of Asthma 3945 Monoclonal Antibodies in the Treatment of COPD 3986 Challenges in Pulmonary Disease 4007 Conclusions 402CHAPTER 20 ANTIBODY-MEDIATED ARTHRITIS AND NEW THERAPEUTIC AVENUESKutty Selva Nandakumar 4071 Autoantibodies in Rheumatoid Arthritis 4072 Role of Cartilage Antigen-Specific Antibodies in Inducing Arthritis 4083 Arthritis Mediation Through Antibodies Recognizing Citrullinated Antigens 4134 Regulation at the Effector Level 4145 Cartilage Damage Independent of Inflammatory Mediators 4146 pathogenicity of GPI-Specific Antibodies 4157 Therapeutic Cleavage of Arthritogenic Antibodies 4158 Arthritis Attenuation Though Removal of Specific Sugars on IgG 417CHAPTER 21 IMMUNONANOPARTICLES FOR NUCLEAR IMAGING AND RADIOTHERAPYOren Giladi and Simon Benita 4271 Radioisotopes and Radiopharmaceuticals 4272 Radiolabeled Antibodies 4323 Radiolabeled Nanoparticles 4374 Future Perspectives and Conclusions 449CHAPTER 22 MONOCLONAL ANTIBODIES IN THE TREATMENT OF ASTHMAGlenn J. Whelan 4571 Introduction 4572 IgE 4583 TNFα 4604 IL-5 4625 IL-9 4646 IL-4 and IL-13 4657 Targeting the T-cell 4678 Conclusions 468References 469INDEX 473