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Drug Delivery

Principles and Applications
Wiley Series in Drug Discovery and Development 2. Aufl.

von: Binghe Wang, Longqin Hu, Teruna J. Siahaan
132,99 €
Verlag:	Wiley
Format:	EPUB
Veröffentl.:	09.03.2016
ISBN/EAN:	9781118833308
Sprache:	englisch
Anzahl Seiten:	720

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Beschreibungen

Titelbeschreibung

Following its successful predecessor, this book covers the fundamentals, delivery routes and vehicles, and practical applications of drug delivery. In the 2nd edition, almost all chapters from the previous are retained and updated and several new chapters added to make a more complete resource and reference. • Helps readers understand progress in drug delivery research and applications • Updates and expands coverage to reflect advances in materials for delivery vehicles, drug delivery approaches, and therapeutics • Covers recent developments including transdermal and mucosal delivery, lymphatic system delivery, theranostics • Adds new chapters on nanoparticles, controlled drug release systems, theranostics, protein and peptide drugs, and biologics delivery

Inhaltsverzeichnis

List of Contributors xvii Preface xxi 1 Factors that Impact the Developability of Drug Candidates 1 Chao Han and Binghe Wang 1.1 Challenges Facing the Pharmaceutical Industry 1 1.2 Factors that Impact Developability 5 1.2.1 Commercial Goal 5 1.2.2 The Chemistry Efforts 6 1.2.3 Biotechnology in the Discovery of Medicine 7 1.2.4 Target Validation in Animal Models 8 1.2.5 Drug Metabolism and Pharmacokinetics 9 1.2.6 Preparation for Pharmaceutical Products 11 1.3 Remarks on Developability 12 1.4 Drug Delivery Factors that Impact Developability 13 References 15 2 Physiological, Biochemical, and Chemical Barriers to Oral Drug Delivery 19 Paul Kiptoo, Anna M. Calcagno, and Teruna J. Siahaan 2.1 Introduction 19 2.2 Physiological Barriers to Drug Delivery 20 2.2.1 Paracellular Pathway 22 2.2.2 Transcellular Pathway 25 2.3 Biochemical Barriers to Drug Delivery 25 2.3.1 Metabolizing Enzymes 25 2.3.2 Transporters and Efflux Pumps 27 2.4 Chemical Barriers to Drug Delivery 28 2.4.1 Hydrogen?]Bonding Potential 28 2.4.2 Other Properties 29 2.5 Drug Modifications to Enhance Transport Across Biological Barriers 29 2.5.1 Prodrugs and Structural Modifications 29 2.5.2 Formulations 30 2.6 Conclusions 31 Acknowledgment 31 References 31 3 Physicochemical Properties, Formulation, and Drug Delivery 35 Dewey H. Barich, Mark T. Zell, and Eric J. Munson 3.1 Introduction 35 3.2 Physicochemical Properties 36 3.2.1 Solubility 37 3.2.2 Stability 40 3.3 Formulations 42 3.3.1 Processing Steps 42 3.3.2 Influence of Physicochemical Properties on Drugs in Formulations 43 3.3.3 Other Issues 43 3.4 Drug Delivery 43 3.4.1 Duration of Release 44 3.4.2 Site of Administration 45 3.4.3 Methods of Administration 46 3.5 Conclusion 47 References 47 4 Targeted Bioavailability: A Fresh Look at Pharmacokinetic and Pharmacodynamic Issues in Drug Discovery and Development 49 Christine Xu 4.1 Introduction 49 4.2 Target Bioavailability 50 4.3 Drug Delivery Trends and Targets Related to PK and PD 51 4.4 PK–PD in Drug Discovery and Development 51 4.5 Source of Variability of Drug Response 55 4.6 Recent Development and Issues of Bio?]Analytical Methodology 57 4.7 Mechanistic PK–PD Models 58 4.8 Summary 60 References 60 5 The Role of Transporters in Drug Delivery and Excretion 62 Marilyn E. Morris and Xiaowen Guan 5.1 Introduction 62 5.2 Drug Transport in Absorption and Excretion 63 5.2.1 Intestinal Transport 63 5.2.2 Hepatic Transport 64 5.2.3 Renal Transport 67 5.2.4 BBB Transport 67 5.3 ABC (ATP?]Binding Cassette) Transporter Family 67 5.3.1 P?]Glycoprotein (ABCB1) 67 5.3.2 Multidrug Resistance?]Associated Proteins (ABCC) 71 5.3.3 Breast Cancer Resistance Protein (ABCG2) 74 5.3.4 Other ABC Transporters 76 5.4 SlC (Solute Carrier) Transporter Family 76 5.4.1 Organic Anion Transporting Polypeptides (SLCO) 76 5.4.2 Organic Anion Transporters (SLC22A) 80 5.4.3 Organic Cation Transporters (SLC22) 81 5.4.4 Multidrug and Toxin Extrusion Transporters (SLC47A) 83 5.4.5 Monocarboxylate Transporters (SLC16 and SLC5) 84 5.4.6 Peptide Transporters (SLC15A) 86 5.4.7 Other SLC Transporters 88 5.5 Conclusions 88 Acknowledgment 88 References 89 6 Intracellular Delivery and Disposition of Small?]Molecular?]Weight Drugs 103 Jeffrey P. Krise 6.1 Introduction 103 6.2 The Relationship between the Intracellular Distribution of a Drug and its Activity 104 6.3 The Relationship between the Intracellular Distribution of a Drug and its Pharmacokinetic Properties 104 6.4 Overview of Approaches to Study Intracellular Drug Disposition 105 6.4.1 Fluorescence Microscopy 106 6.4.2 Organelle Isolation 106 6.4.3 Indirect Methods 107 6.5 The Accumulation of Drugs in Mitochondria, Lysosomes, and Nuclei 108 6.5.1 Mitochondrial Accumulation of Drugs 108 6.5.2 Lysosomal Accumulation of Drugs 112 6.5.3 Nuclear Accumulation of Drugs 122 6.6 Summary and Future Directions 123 References 124 7 Cell Culture Models for Drug Transport Studies 131 Irina Kalashnikova, Norah Albekairi, Shariq Ali, Sanaalarab Al Enazy, and Erik Rytting 7.1 Introduction 131 7.2 General Considerations 132 7.3 Intestinal Epithelium 133 7.3.1 The Intestinal Epithelial Barrier 133 7.3.2 Intestinal Epithelial Cell Culture Models 134 7.4 The Blood–Brain Barrier 135 7.4.1 The Blood–Brain Endothelial Barrier 135 7.4.2 BBB Cell Culture Models 136 7.5 Nasal and Pulmonary Epithelium 137 7.5.1 The Respiratory Airway Epithelial Barrier 137 7.5.2 The Nasal Epithelial Barrier and Cell Culture Models 138 7.5.3 The Airway Epithelial Barrier and Cell Culture Models 139 7.5.4 The Alveolar Epithelial Barrier and Cell Culture Models 140 7.6 The Ocular Epithelial and Endothelial Barriers 141 7.6.1 The Corneal and Retinal Barriers 141 7.6.2 Cell Culture Models of Ocular Epithelium and Endothelium 142 7.7 The Placental Barrier 142 7.7.1 The Syncytiotrophoblast Barrier 142 7.7.2 Trophoblast Cell Culture Models 143 7.8 The Renal Epithelium 143 7.8.1 The Renal Epithelial Barrier 143 7.8.2 Renal Epithelial Cell Culture Models 144 7.9 3D In Vitro Models 145 7.10 Conclusions 146 References 146 8 Intellectual Property and Regulatory Issues in Drug Delivery Research 152 Shahnam Sharareh and Wansheng Jerry Liu 8.1 Introduction 152 8.2 Pharmaceutical Patents 153 8.3 Statutory Requirements for Obtaining a Patent 154 8.3.1 Patentable Subject Matter 154 8.3.2 Novelty 155 8.3.3 Nonobviousness 155 8.4 Patent Procurement Strategies 157 8.5 Regulatory Regime 158 8.6 FDA Market Exclusivities 160 8.7 Regulatory and Patent Law Linkage 162 References 162 9 Presystemic and First?]Pass Metabolism 164 Qingping Wang and Meng Li 9.1 Introduction 164 9.2 Hepatic First?]Pass Metabolism 165 9.2.1 Hepatic Enzymes 166 9.3 Intestinal First?]Pass Metabolism 170 9.3.1 Intestinal Enzymes 170 9.3.2 Interplay of Intestinal Enzymes and Transporters 174 9.4 Prediction of First?]Pass Metabolism 174 9.4.1 In vivo Assessment of First?]Pass Metabolism 174 9.4.2 In vitro Assessment of First?]Pass Metabolism 175 9.4.3 In vitro–in vivo Prediction 177 9.4.4 In Silico Approach 178 9.5 S trategies for Optimization of Oral Bioavailability 178 9.6 Summary 179 References 180 10 Pulmonary Drug Delivery: Pharmaceutical Chemistry and Aerosol Technology 186 Anthony J. Hickey 10.1 Introduction 186 10.2 Aerosol Technology 187 10.2.1 Particle Production 187 10.2.2 Propellant?]Driven Metered?]Dose Inhalers 188 10.2.3 Dry Powder Inhalers 188 10.2.4 Nebulizer 190 10.3 Disease Therapy 190 10.3.1 Asthma 190 10.3.2 Emphysema 193 10.3.3 Cystic Fibrosis 195 10.3.4 Other Locally Acting Agents 195 10.3.5 Systemically Acting Agents 196 10.4 Formulation Variables 196 10.4.1 Excipients 197 10.4.2 Interactions 199 10.4.3 Stability 200 10.5 Regulatory Considerations 200 10.6 Future Developments 201 10.7 Conclusion 201 References 202 11 Transdermal Delivery of Drugs Using Patches and Patchless Delivery Systems 207 Tannaz Ramezanli, Krizia Karry, Zheng Zhang, Kishore Shah, and Bozena Michniak?]Kohn 11.1 Introduction 207 11.2 Transdermal Patch Delivery Systems 208 11.2.1 Definition and History of Patches 208 11.2.2 Anatomy and Designs of Patches 209 11.3 Patchless Transdermal Drug Delivery Systems 211 11.3.1 First?]Generation Systems 212 11.3.2 Second?]Generation Systems 212 11.3.3 Third?]Generation Systems 214 11.4 Recent Advances in Transdermal Drug Delivery 216 11.4.1 Frontier in Transdermal Drug Delivery: Transcutaneous Immunization via Microneedle Techniques 216 11.4.2 Patchless Transdermal Delivery: The PharmaDur “Virtual Patch” 219 11.5 Summary 221 References 222 12 Prodrug Approaches to Drug Delivery 227 Longqin Hu 12.1 Introduction 227 12.2 Basic Concepts: Definition and Applications 228 12.2.1 Increasing Lipophilicity to Increase Systemic Bioavailability 228 12.2.2 S ustained?]Release Prodrug Systems 231 12.2.3 Improving Gastrointestinal Tolerance 232 12.2.4 Improving Taste 232 12.2.5 Diminishing Gastrointestinal Absorption 233 12.2.6 Increasing Water Solubility 233 12.2.7 Tissue Targeting and Activation at the Site of Action 234 12.3 Prodrug Design Considerations 238 12.4 Prodrugs of Various Functional Groups 241 12.4.1 Prodrugs of Compounds Containing??COOH or??OH 241 12.4.2 Prodrugs of Compounds Containing Amides, Imides, and Other Acidic NH 246 12.4.3 Prodrugs of Amines 249 12.4.4 Prodrugs for Compounds Containing Carbonyl Groups 255 12.5 Drug Release and Activation Mechanisms 258 12.5.1 Cascade Release Facilitated by Linear Autodegradation Reactions 260 12.5.2 Cascade Release Facilitated by Intramolecular Cyclization Reactions 262 12.5.3 Cascade Activation through Intramolecular Cyclization to form Cyclic Drugs 264 12.6 Prodrugs and Intellectual Property Rights—Two Court Cases 266 References 268 13 Liposomes as Drug Delivery Vehicles 272 Guijun Wang 13.1 Introduction 272 13.2 Currently Approved Liposomal Drugs in Clinical Applications 273 13.3 Conventional and Stealth Liposomes 276 13.4 Stimuli?]Responsive Liposomes or Triggered?]Release Liposomes 277 13.4.1 General Mechanism of Triggered Release 277 13.4.2 Thermo?]Sensitive Liposomes 278 13.4.3 pH?]Sensitive Liposomes 279 13.4.4 Photo?]Triggered Liposomes 282 13.4.5 Triggered Release Controlled by Enzymes 287 13.5 Targeted Liposomal Delivery 289 13.6 Hybrid Liposome Drug Delivery System 291 13.7 Conclusions and Future Perspectives 293 References 293 14 Nanoparticles as Drug Delivery Vehicles 299 Dan Menasco and Qian Wang 14.1 Introduction 299 14.1.1 General DDV Properties 300 14.1.2 The DDV Core: Therapeutic Loading, Release, and Sensing 301 14.1.3 DDV Targeting: Ligand Display 305 14.1.4 DDV Size and Surface: Clearance and the EPR Effect 308 14.2 O rganic DDVs 308 14.2.1 Polymer-Based Nanocarriers 308 14.2.2 Polymeric Micelles 310 14.2.3 Dendrimers 314 14.3 Inorganic DDVs: Metal?] and Silica?]Based Systems 320 14.3.1 Inorganic DDVs: Mesoporous Silica Nanoparticles 322 14.3.2 Inorganic DDVs: Gold Nanoparticles 324 14.4 Conclusion 330 References 330 15 Evolution of Controlled Drug Delivery Systems 336 Krishnaveni Janapareddi, Bhaskara R. Jasti, and Xiaoling Li 15.1 Introduction 336 15.2 Biopharmaceutics and Pharmacokinetics 337 15.3 Material Science 341 15.4 Proteins, Peptides and Nucleic Acids 343 15.5 Discovery of New Molecular Targets—Targeted Drug Delivery 345 15.6 Microelectronics and Microfabrication Technologies 347 15.7 Conclusion 349 References 349 16 Pathways for Drug Delivery to the Central Nervous System 353 Ngoc H. On, Vinith Yathindranath, Zhizhi Sun, and Donald W. Miller 16.1 Introduction 353 16.1.1 Cellular Barriers to Drug Delivery in the CNS 354 16.1.2 General Approaches for Increasing Brain Penetration of Drugs 356 16.2 Circumventing the CNS Barriers 356 16.2.1 Intracerebroventricular Injection 357 16.2.2 Intracerebral Administration 357 16.2.3 Intranasal Delivery Route 358 16.3 Transient BBB Disruption 359 16.3.1 Osmotic BBB Disruption 359 16.3.2 Pharmacological Disruption of the BBB 360 16.4 Transcellular Delivery Routes 364 16.4.1 Solute Carrier Transport Systems in the BBB 364 16.4.2 Adenosine Triphosphate?]Binding Cassette Transport Systems in the BBB 369 16.4.3 Vesicular Transport in the BBB 370 16.5 Conclusions 375 References 375 17 Metabolic Activation and Drug Targeting 383 Xiangming Guan 17.1 Introduction 383 17.2 Anticancer Prodrugs and their Biochemical Basis 384 17.2.1 Tumor?]Activated Anticancer Prodrugs Based on Hypoxia 385 17.2.2 Tumor?]Activated Prodrugs Based on Elevated Peptidases or Proteases 401 17.2.3 Tumor?]Activated Prodrugs Based on Enzymes with Elevated Activity at Tumor Sites 413 17.3 Antibody?] and Gene?]Directed Enzyme Prodrug Therapy 420 17.3.1 ADEPT 421 17.3.2 GDEPT 425 17.4 Summary 429 References 429 18 Targeted Delivery of Drugs to the Colon 435 Anil K. Philip and Sarah K. Zingales 18.1 Introduction 435 18.2 Microbially Triggered Release 437 18.2.1 Azo?]Linked Compounds 437 18.2.2 Amino Acid Conjugates 440 18.2.3 Sugar?]Derived Prodrugs 440 18.3 pH?]Sensitive Polymers for Time?]Dependent Release 442 18.4 Osmotic Release 443 18.5 Pressure?]Controlled Delivery 443 18.6 Nanoparticle Approaches 444 18.7 Conclusion 446 Acknowledgment 446 References 447 19 Receptor?]Mediated Drug Delivery 451 Chris V. Galliford and Philip S. Low 19.1 Introduction 451 19.2 Selection of a Receptor for Drug Delivery 454 19.2.1 Specificity 454 19.2.2 Receptor Internalization/Recycling 455 19.3 Design of a Ligand–Drug Conjugate 455 19.3.1 Linker Chemistry 455 19.3.2 Selection of Ligands 457 19.3.3 Selection of Therapeutic Drug 457 19.4 Folate?]Mediated Drug Delivery 458 19.4.1 Expression of FRs in Malignant Tissues 459 19.4.2 Expression of FRs in Normal Tissues 460 19.4.3 Applications of Folate?]Mediated Drug Delivery 461 19.5 Conclusions 467 Acknowledgments 467 References 467 20 Protein and Peptide Conjugates for Targeting Therapeutics and Diagnostics to Specific Cells 475 Barlas Büyüktimkin, John Stewart, Jr., Kayann Tabanor, Paul Kiptoo, and Teruna J. Siahaan 20.1 Introduction 475 20.2 Radiolabeled Antibodies for Cancer Treatment 479 20.3 Antibody–Drug Conjugate 480 20.3.1 Sites of Conjugation on mAbs, Linkers, and Drugs 481 20.4 Non?]Antibody?]Based Protein–Drug Conjugates 486 20.5 Peptibody 488 20.6 Protein Conjugates for Diagnostics 489 20.7 Peptide–Drug Conjugates 491 20.8 Challenges in Analyzing Conjugates 494 20.9 Conclusions 497 References 497 21 Drug Delivery to the Lymphatic System 503 Qiuhong Yang and Laird Forrest 21.1 Introduction 503 21.2 Anatomy and Physiology of the Lymphatic System 504 21.2.1 Lymph 504 21.2.2 Lymphatic Vessels 504 21.2.3 Lymph Nodes 506 21.2.4 Lymph Organs 508 21.3 Influence of Physicochemical Characteristics of Drug Carriers on Lymphatic Uptake and Transport 509 21.3.1 Size 509 21.3.2 Surface Charge 511 21.3.3 Hydrophobicity 513 21.4 Carriers for Lymphatic Drug Delivery 513 21.4.1 Liposomes 515 21.4.2 Lipid?]Based Emulsions and Nanoparticles 519 21.4.3 Polymer?]Based Carriers 524 21.5 Administration Routes for Lymphatic Delivery 528 21.5.1 Intestinal 528 21.5.2 Pulmonary 529 21.5.3 Subcutaneous 531 21.5.4 Intraperitoneal 535 21.6 Lymphatic?]Targeting Vaccination 536 21.7 Conclusions 538 References 539 22 The Development of Cancer Theranostics: A New Emerging Tool Toward Personalized Medicine 549 Hongying Su, Yun Zeng, Gang Liu, and Xiaoyuan Chen 22.1 Introduction 549 22.2 Imaging?]Guided Drug Delivery and Therapy 551 22.3 Optical Imaging-Based Theranostics 553 22.3.1 NIR Fluorescence Imaging 553 22.3.2 Bioluminescence Imaging 556 22.3.3 Gold Nanoparticle as a Theranostics Platform 557 22.4 MRI?]Based Theranostics 558 22.5 Nuclear Imaging-Based Theranostics 559 22.6 Ultrasound?]Based Theranostic Platform 563 22.7 Multimodality Imaging-Based Theranostic Platform 564 22.7.1 PET/CT 565 22.7.2 MRI/Optical 566 22.7.3 MRI/PET 566 22.8 Conclusion and Future Perspectives 567 Acknowledgments 569 References 569 23 Intracellular Delivery of Proteins and Peptides 576 Can Sarisozen and Vladimir P. Torchilin 23.1 Introduction 576 23.2 Intracellular Delivery Strategies of Peptides and Proteins 579 23.3 Concepts in Intracellular Peptide and Protein Delivery 580 23.3.1 Longevity in the Blood 580 23.3.2 Cellular Uptake Pathways 582 23.3.3 Endosomal Escape 585 23.4 Peptide and Protein Delivery to Lysosomes 589 23.5 Receptor?]Mediated Intracellular Delivery of Peptides and Proteins 590 23.5.1 Transferrin Receptor–Mediated Delivery 590 23.5.2 Folate Receptor–Mediated Delivery 593 23.6 Transmembrane Delivery of Peptides and Proteins 595 23.6.1 Well Studied Classes of CPPs for Peptide and Protein Delivery 595 23.6.2 Cellular Uptake Mechanisms of CPPs 596 23.6.3 CPP?]Mediated Delivery of Peptides and Proteins 599 23.6.4 CPP?]Modified Carriers for Intracellular Delivery of Peptides and Proteins 601 23.7 Conclusion 602 References 602 24 Vaccine Delivery: Current Routes of Administration and Novel Approaches 623 Neha Sahni, Yuan Cheng, C. Russell Middaugh, and David B. Volkin 24.1 Introduction 623 24.2 Parenteral Administration of Vaccines 625 24.2.1 Currently Available Vaccines and Devices for Intramuscular and Subcutaneous Delivery 625 24.2.2 Currently Available Intradermal Vaccines and Associated Delivery Devices 629 24.2.3 Novel Devices for Parenteral Injection 630 24.2.4 Novel Formulations and Delivery Approaches for Parenteral Injection 632 24.3 Oral Delivery of Vaccines 634 24.3.1 Currently Available Orally Administered Vaccines 634 24.3.2 Novel Formulations and Delivery Approaches for Oral Administration 635 24.4 Nasal and Aerosol Delivery of Vaccines 639 24.4.1 Currently Available Nasally Administered Vaccines 639 24.4.2 Novel Devices and Formulations for Nasal Administration 639 24.4.3 Devices and Delivery Systems for AerosolAdministration of Vaccines 642 24.5 Conclusions 643 References 644 25 Delivery of Genes and Oligonucleotides 655 Charles M. Roth 25.1 Introduction 655 25.2 Systemic Delivery Barriers 656 25.2.1 Viruses: Learning from Nature 657 25.2.2 Materials for Nucleic Acid Delivery 658 25.2.3 Characterization of Nanoparticles 659 25.2.4 Targeted Delivery of Nucleic Acids 662 25.3 Cellular Delivery Barriers 663 25.3.1 Endosomal Escape 663 25.3.2 Vector Unpackaging 665 25.4 Current and Future Approaches to Nucleic Acid Delivery 666 25.4.1 Vectors in the Clinic 666 25.4.2 Combinatorial Chemistry Approaches 667 25.4.3 Polymer–Lipid Nanocomposites 667 25.5 Summary and Future Directions 668 References 668 Index 674

Autorenportrait

Binghe Wang, PhD, is Regents’ Professor of Chemistry and Associate Dean for Natural and Computational Sciences at Georgia State University as well as Georgia Research Alliance Eminent Scholar in Drug Discovery. He is Editor-in-Chief of the journal Medicinal Research Review and founding series editor of the Wiley Series in Drug Discovery and Development. He has published over 230 papers in medicinal chemistry, pharmaceutical chemistry, new diagnostics, and chemosensing. Longqin Hu, PhD, is Professor of Medicinal Chemistry and Director of the Graduate Program in Medicinal Chemistry at Rutgers University. Among his major research interests are the synthesis and evaluation of anticancer prodrugs for the targeted activation in tumor tissues and the discovery of novel small molecule inhibitors of protein-protein interactions. He has published over 80 papers and 8 patents in bioorganic and medicinal chemistry. Teruna Siahaan, PhD, is a Professor and Associate Chair of the Department of Pharmaceutical Chemistry and serves as the Director of the NIH Biotechnology Training Program at the University of Kansas. In addition to co-editing the first edition of Drug Delivery, he has written almost 195 journal papers and book chapters and received the 2014 PhRMA Foundation Award in Excellence in Pharmaceutics.

Back cover copy

An indispensable tool for those working at the front lines of new drug development The development of effective delivery systems is crucial to taking a drug from the discovery and development stages to successful clinical use. The advances of recent years in the pharmaceutical sciences, including from molecular biology and biotechnology, make the challenges of drug delivery higher and the need to train pharmaceutical scientists and students greater. Continuing the legacy of its successful predecessor, the second edition of Drug Delivery gets readers quickly up to speed on both the principles and latest applications in the increasingly important field of drug delivery. Contributions from leading international experts allows Drug Delivery to cover the entire field in a systematic yet concise way. It begins with an in-depth review of key fundamentals that include developability factors, physiochemical and biological barriers, drug delivery pathways, pharmacokinetics and pharmacodynamics, and regulations and intellectual property. The remainder of the book systematically examines a host of specific subjects, including: Routes of drug administration Approaches to improve delivery Targeted drug delivery systems Delivery of macromolecular drugs