Biological barriers to protein delivery

목차 (Table of Contents)

• 목차
• Part Ⅰ. Cellular Barriers
• Chapter 1 The Paracellular pathway : A Small Version of the Kidney Nephron / Marcelino Cereijido ; Octavio Ruiz ; orenza Gonz$$\acute{a}$$lez-Mariscal ; Rub$$\acute{e}$$n Gerardo Contreras ; Mar$$\acute{i}$$a Susana Balda ; M. R. Garc$$\acute{i}$$a-Villegas
• 1. Introduction = 3
• 2. The Structure of the Tight Junction = 5
• 3. Junctons and Cell-Attaching Molecules That Complement the Role of the Tight Juncton = 9
• 4. The Physiology of the Paracellular Pathway = 10
• 5. Intracellular Structures and Chemical Signals That Control the Assmbly and Sealing of the Tight Junction, and That Regulate Permeation through the Paracellular Route = 12
• 6. Relationship between Tight Junctions and Apical／Basolateral Polarity = 13
• 7. Concluding Remarks = 16
• References = 17
• Chapter 2 Ectopeptidases / Nigel M. Hooper
• 1. Introduction = 23
• 2. Properties of Mammalian Ectopeptidases = 26
• 2.1. Endopeptidases = 26
• 2.2. Aminopeptidases = 27
• 2.3. Carboxypeptidases = 28
• 2.4. Dipeptidyl Peptidase = 29
• 2.5. Peptidyl Dipeptidase = 29
• 2.6. Dipeptidases = 32
• 2.7. Omega peptidases = 32
• 3. Organ, Tissue, and Cellular Distribution of Ectopeptidases = 33
• 4. Concerted Action of Ectopeptidases = 36
• 5. Physiological Functions of Ectopeptidases = 39
• 5.1. Endopeptidase-24.11 = 39
• 5.2. Angiotensin-Converting Enzyme = 40
• 5.3. Membrane Dipeptidase = 41
• 5.4. γ-Glutamyl Transpeptidase = 41
• 6. Conclusions and Future Perspectives = 42
• References = 43
• Chapter 3 Endosomal and Lysosmal Hydrolases / Sandra A. Brockman ; Robert F. Murphy
• 1. Introduction = 51
• 1.1. Endosome = 52
• 1.2. Lysosome = 53
• 2. Acidification of Endosomes and Lysosomes = 53
• 2.1. pH Measurements = 53
• 2.2. pH Regulaton = 54
• 3. Transient and Stable Compatment Models for Endosomes and Lysosomes = 55
• 4. Enzyme Activities of Endosomes and Lysosomes = 55
• 4.1. Distribution of Hydrolases between Endosomes and Lysosomes = 55
• 4.2. Proteases = 56
• 4.3. Disulfide Bond Reduction = 58
• 4.4. Glycosidases = 60
• 4.5. Sulfatases = 61
• 4.6. Phosphatases = 62
• 4.7. Lipases = 62
• 5. Processing of physiological Ligands = 63
• 6. Antigen presentation = 64
• 7. Conclusions = 64
• References = 65
• Chapter 4 Protein Uptake and Cytoplasmic Access in Animal Cells / Bo van Deurs ; Steen H. Hansen ; Sjur Olsnes ; Kirsten Sandvig
• 1. Introduction = 71
• 2. Entry of proteins into the Cytosol = 72
• 3. Endocytic Uptake = 74
• 4. Intracellular Sortng and Transport = 81
• 4.1. Endosomes as the Site of Intracellular Sorting = 81
• 4.2. Transport to Lysosomes = 83
• 4.3. Recycling = 85
• 4.4. Transcytosis = 88
• 4.5. Transport to the Golgi Complex = 91
• 5. Translocation across Internal Membrane Systems = 92
• 6. Perspectives = 93
• Reference = 94
• Part Ⅱ. Epithelial Barriers
• Chapter 5 Transepithelial Transport of Proteins by Intestinal Epithelial Cells / Marian R. Neutra ; Jean-Pierre Kraehenbuhl
• 1. Introduction = 107
• 2. Transepithelial Transport Mechanisms = 108
• 2.1. Establishment and maintenance of Cell Polarity = 109
• 2.2. Endocytosis and Sorting into the Transcytotic Pathway = 110
• 2.3. Mechanism of Transcytosis = 111
• 2.4. Role of the Cytoskeleton in Vesicular Traffic = 113
• 3. membrane Traffic in Intestinal Enterocytes = 114
• 3.1. Mechanisms of Antigen Exclusion by Enterocytes = 114
• 3.2. Membrane Traffic in Vacuolated Enterocytes = 115
• 3.3. Membrane Traffic in Adult Enterocytes = 116
• 4. Membrane Traffic in Intestinal M. Cells = 118
• 4.1. Induction of the M Cell Phenotype = 118
• 4.2. Adherence of Macromolecules of M Cell Apical Membranes = 118
• 4.3. Adherence of Microorganisms to M Cells = 119
• 4.4. Transcytosis by M Cells = 120
• 5. Conclusion = 121
• References = 122
• Chapter 6 Intraoral Peptide Absorpton / Hans P. Merkle ; Gregor J. M. Wolany
• 1. Introducton = 131
• 2. The Structure of the Oral Epithelium = 132
• 2.1. Anatomy of the Oral Cavity = 132
• 2.2. Histology of the Buccal Mucasa = 132
• 2.3. Biochemistry of the Buccal Mucosa = 135
• 2.4. Saliva and Mucus = 136
• 3. Experimental Techniques for Studying oral Absorption = 137
• 3.1. Human Assays = 137
• 3.2. Animal Models = 139
• 3.3. In Vitro Techniques = 140
• 4. Literature Survey on Intraoral Peptide Absorption = 140
• 5. Mechanisms of Peptide and Protein Absorption = 144
• 6. Strategies for Enhancing Intraoral peptide Absorption = 148
• 6.1. Dosage Form Design and Patent Review = 148
• 6.2. Chemical Strategies for Enhancing Buccal peptide Absorption = 151
• 7. Conclustions = 153
• References = 155
• Chapter 7 Macromolecular Transport across nasal and Respiratory Epithelia / Larry G. Johnson ; Richard C. Boucher
• 1. Introduction = 161
• 2. Anatomy of the Respiratory Epithelia = 162
• 2.1. Airway Epithelia = 162
• 2.2. Alveolar Epithelia = 163
• 3. Evidence for Paracellular Flow of peptides and Proteins = 164
• 3.1. Diffusion through Pores = 164
• 3.2. Regulation of Paracellular permeability = 165
• 4. Evidence for Transcellular Flow of peptides and Proteins = 168
• 4.1. Nasal Epithelia = 168
• 4.2. Conducting Airway Epithelia = 168
• 4.3. Alveolar Epithelia = 169
• 5. Potential mechanisms of Transcellular Flow = 170
• 5.1. Receptor-Mediated Endocytosis in Airways = 170
• 5.2. Adsorptive Endocytosis in Airways = 171
• 5.3. Sodium-Dependent Amino Acid Cotransport in Alveolar Epithelia = 172
• 6. Role of Macrophage Surveillance = 173
• 7. Summary = 173
• References = 174
• Chapter 8 Dermal Absorption of Peptides and Proteins / Ajay K. Banga ; Yie W. Chien
• 1. Introduction = 179
• 2. Dermal Transport = 180
• 2.1. Dermal Anatomy = 180
• 2.2. Transport Mechanisms = 182
• 3. Dermal Barriers to peptide／Protein Delivery = 183
• 3.1. Metabolic／Enzymatic Barrier = 183
• 3.2. Physical Barrier = 184
• 3.3. Microbial Barrier = 185
• 4. Strategies for Dermal Delivery of Peptides／Proteins = 185
• 4.1. Noninvasive Delivery through Intack Skin = 186
• 4.2. Invasive Delivery through Broken Skin = 191
• 5. Drug Delivery Design = 193
• 6. prospects of Dermal Delivery of Peptides／Proteins = 194
• References = 195
• Chapter 9 Rectal and Vaginal Absorption of Peptides and Proteins / Shozo Muranishi ; Akira Yamamoto ; Hiroaki okada
• 1. Introduction = 199
• 2. Rectal Barrier = 200
• 2.1. Anatomy and Physiology of the Rectum = 200
• 2.2. Rectal Absorption of Peptides and Proteins = 201
• 2.3. Conclustion = 211
• 3. Vaginal Barrier = 211
• 3.1. Anatomy and Physiology of the Vagina = 211
• 3.2. Vaginal Absorption of Peptides and Proteins = 214
• 3.3. Conclusions = 221
• References = 222
• Part Ⅲ. Vascular Barriers
• Chapter 10 Vascular Endothelial Barrier and Its Regulation / Asrar B. Malik ; Alma Siflinger-Birnboim
• 1. Introduction = 231
• 2. Routes of Endothelial transport = 232
• 3. Starling's Equation = 233
• 4. Endothelial Cell Monolayers in Culture = 234
• 5. Effect of Molecular Size on Endothelial permeability : The "Pore" Theory = 238
• 6. Effects of Cellular and Molecular Charge on Endothelial permeability = 240
• 7. Regional Vascular Differences in Endothelium on Endothelial Permeability = 244
• 8. Active Transport of Albumin = 246
• 9. Receptor-Mediated Albumin Transcytosis = 246
• 10. Mechanisms of Increased Endothelial permeability = 250
• 10.1. Characteristics of Increased Endothelial permeability = 250
• 10.2. Cytoskeletal Alterations = 251
• 10.3. Intracellular Ca$$^{2+}$$ Shits = 252
• 10.4. Protein Kinase C Activation = 254
• 10.5. Basement Membrane and matrix Components = 256
• 11. Decreases in Endothelial permeability Induced by Cyclic Nucleotides = 257
• 12. Endothelial Water permeability = 257
• 13. Conclusions = 259
• References = 260
• Chapter 11 Transcytosis of Macromolecules through the Blood-Brain Fluid Barriers in Vivo / Richard D. Broadwell
• 1. Introduction = 269
• 2. Endocytic processes Defined = 271
• 3. Characteristics of the Blood-Brain Fluid Barriers = 273
• 4. Extracellular Pathways Circumventing the Blood-Brain Fluid Barriers = 275
• 5. Circumventing the Blood-Brain Fluid Barriers through Intracellular Pathways and Transcytosis = 281
• 5.1. Fluid-Phase Endocytosis = 281
• 5.2. Adsorptive Transcytosis = 282
• 5.3. Receptor-Mediated Transcytosis = 286
• 6. The Enigma of Transcytosis through the Blood-Brain Barrier = 289
• 7. Intracerebral Transplants and the Blood-Brain Barrier = 290
• 8. Summary and Conclusions = 290
• References = 291
• Part Ⅳ. Elimination Barriers
• Chapter 12 Renal Uptake and Disposal of Proteins and Peptides / Ralph Rabkin ; David C. Dahl
• 1. Introduction = 299
• 2. Methods of Study = 302
• 3. Vascular Elimination Barriers = 305
• 3.1. Glomerular Vascular Barrier = 305
• 3.2. peritubular Vascular Barrier = 310
• 4. Extravascular pathways in the Kidney = 312
• 4.1. Apical Tubular Cell Uptake and Urinary Excretion = 312
• 4.2. Basolateral Tubular Cell Protein Uptake = 318
• 5. Renal handing of Bioactive Proteins and Peptides : Representative Examples = 320
• 5.1. Insulin = 320
• 5.2. Atrial Natriuretic Peptide = 323
• 5.3. Angiotesin = 325
• 6. Renal Handling of Glycoproteins = 326
• 7. Effect of Renal Failure on Elimination of Proteins = 327
• References = 329
• Chapter 13 Mechanisms for the Hepatic Clearance of Oligopeptides and Proteins : Inplications for Rate of Elimination, Bioavailability, and Cell-Specific Drug Delivery to the Liver / Dirk K. F. Meijer ; Kornelia Ziegler
• 1. Scope of the Review = 339
• 2. The Liver = 340
• 2.1. Organizational Aspects = 340
• 2.2. Functional Liver Structure = 342
• 2.3. Cell Types of the Liver = 343
• 2.4. Protein Synthesis in the Liver = 344
• 2.5. Degradation of proteins and peptides in the Liver = 344
• 3. Mechanisms for hepatic Uptake of Proteins and Oligopeptides = 346
• 3.1. Carrier-Mediated membrane transport = 346
• 3.2. Multiplicity in hepatic Transport Mechanisms = 349
• 4. Carrier- and Non-Carrier-Mediated uptake of Oligopeptides by the Liver = 351
• 4.1. Introduction = 351
• 4.2. Peptide Transport by Bile Acid Carriers = 353
• 4.3. Mechanisms and Energization of the Peptide Transporters = 356
• 4.4. Driving Forces for hepatic Uptake of peptides = 356
• 4.5. Structure-Kinetic Relationships of peptides = 357
• 4.6. Carrier proteins of the Peptide Uptake Systems = 359
• 4.7. Energy-Dependent Carrier-Mediated peptide Transport Not Related to Bile Acid Carriers = 360
• 4.8. Peptide Uptake by Passive Lipoid Permeation = 360
• 4.9. Current Knowledge and Physiological Meaning of Peptide Clearance by the Liver = 361
• 5. Mechanisms for Hepatic Clearance of Proteins = 362
• 5.1. Endocytosis and Phagocytosis = 362
• 5.2. Receptor-Mediated Endocytosis in Various Cell Types of the Liver = 364
• 5.3. Particle Endocytosis by Opsonin- and Receptor-Mediated Mechanisms = 366
• 5.4. Endocytosis of Polymeric IgA = 368
• 5.5. Endocytosis of Proteins with a Net Positive Charge = 369
• 5.6. Receptors for proteins with a Net negative Charge = 369
• 5.7. Galactosyl (Asialoglycoprotein) Receptors for Endocytosis in Hepatocytes = 371
• 5.8. Galactosyl Receptors in Other Cell Types = 374
• 5.9. mannosyl Receptors for Endocytosis in Sinusoidal Cell Types = 375
• 5.10. Influence of Sugar Density and Clustering on Endocytosis = 376
• 6. Hepatic Clearance of Therapeutic Proteins and Oligopeptides : An Integration of Concepts = 378
• 6.1. Chemical and Physiological Factors = 378
• 6.2. Manipulations of the Hepatic Clearance of peptides = 382
• 7. Protein Transport in Relation to Drug Trageting in the Liver = 383
• 7.1. Introduction = 383
• 7.2. Potential Carrier Systems for Liver Targeting = 384
• 7.3. Lysosomal Release of Active Drug from the Protein Carrier = 386
• 7.4. preparation of (Glyco)protein-Drug Conjugates = 386
• 7.5. Current Achievements in Drug Targeting to the Liver with Protein Carriers = 387
• References = 392
• Chapter 14 The Immune System as a Barrier to Delivery of Protein Therapeutics / Michael W. Konrad
• 1. Introduction = 409
• 2. Structure of the Immune System = 410
• 2.1. Antibodies and B Cells = 410
• 2.2. T Cells = 411
• 3. Assays = 412
• 3.1. Antigen-Specific Antibody = 412
• 3.2. Neutralizing Antibody = 413
• 3.3. T Cell Activity = 414
• 4. Antitoxin Serum : The First Protein Therapeutic = 415
• 5. Insulin : A paradigm = 416
• 5.1. Introduction and History = 416
• 5.2. Local Immune-Mediated Toxicities = 416
• 5.3. Systemic Immune-Mediated Toxicities = 417
• 5.4. Causes of Insulin Immunogenicity = 419
• 5.5. use of Human Insulin = 420
• 5.6. Etiology of Diabetes : An Autoimmune Disease? = 420
• 6. Factor Ⅷ = 421
• 7. Interferons and Lymphokines = 422
• 7.1. Introduction = 422
• 7.2. Interferon Alpha = 423
• 7.3. Interferon Beta = 425
• 7.4. Inerleukin-2 = 425
• 8. Monoclonal Antibodies and Immunotoxins = 426
• 9. Predicting Immunogenicity = 427
• 9.1. Covalent Structure : Amino Acid Sequence and Glycosylation = 427
• 9.2. Everything Else = 428
• 10. Summary and Conclusion = 429
• Reference = 430
• Part. Ⅴ. Tissue Barriers
• Chapter 15 Extravasation and Interstitial Transport in Tumors / Rakesh K. Jain ; Laurence T. Baxter
• 1. Introduction = 441
• 2. Extravasation = 443
• 2.1. Staling's Law of Fluid Filtration = 443
• 2.2. Transcapillay Exchange = 443
• 2.3. Interstitial Pressure = 446
• 3. Interstitial Transport = 446
• 3.1. Diffusion = 446
• 3.2. Convection = 449
• 3.3. Bindng = 451
• 4. Transport Properties of Tumors = 452
• 4.1. Interstitial Properties = 452
• 4.2. perfusion Characteristics = 453
• 4.3. Role of Necrosis = 454
• 4.4. Role of Tumor Size = 454
• 5. Transport Properties of Proteins = 454
• 5.1. Diffusion Coefficients = 454
• 5.2. Permeability Coefficients = 455
• 5.3. Binding and Metabolism Parameters = 456
• 5.4. Molecular Weight = 458
• 6. Summary and Implications = 459
• 6.1. Summary = 459
• 6.2. Implications for Drug Delivery = 460
• 6.3. Two-Step Approaches = 461
• References = 463
• Chapter 16 Tissue Barriers : Diffusion, Bulk Flow, and Volume Transmission of proteins and Peptides within the Brain / Conrad E. Johanson
• 1. Overview = 467
• 2. Two Major Extracellular Fluids inside the Central nervous System = 468
• 2.1. Large-Cavity Cerebrospinal Fluid(CSF) = 468
• 2.2. Cerebral Interstitial Fluid(ISF) = 468
• 3. Dynamics of the Extracellular Fluid = 469
• 3.1. CSF : Two Major Drainage Routes = 470
• 3.2. ISF : Brain Parenchyma Distributive Pathways = 471
• 3.3. CSF-ISF Exchange across the Ependymal Wall = 472
• 4. Newly Emerging Concepts of Volume Transmission = 473
• 4.1. Classification According to Transmission Distance = 474
• 4.2. Chemophysical Characteristics of the Extracellular Space = 474
• 4.3. Other Factors Modifying Volume Transmission = 475
• 5. Choroid Plexus (CP) : A "Target" and a "Source" in Volume Transmission = 477
• 5.1. CP Receptors for Peptides = 478
• 5.2. CP as a Generator of Protein Signals = 478
• 6. Brain Cells as Targets for Proteinaceous Substances = 479
• 6.1. Types of Growth Factors in Brain = 479
• 6.2. Temporal Expression of Nerve Growth Factor = 479
• 6.3. Boosting the Level of Growth Factors in the CNS = 479
• 6.4. How Cerebral Levels of NGF Can Be Elevated = 480
• 6.5. Time Course of NGF Spreading after Injection into rain = 480
• 7. Prospects for Research on Peptide and Protein Distribution in CNS References = 481
• Referemces = 482
• Index = 487