Schäfer-Korting Drug Delivery

1. Auflage 2010
ISBN: 978-3-642-00477-3
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 197, 501 Seiten

Reihe: Handbook of Experimental Pharmacology

In the view of most experts pharmacology is on drugs, targets, and actions. In the context the drug as a rule is seen as an active pharmaceutical ingredient and not as a complex mixture of chemical entities of a well defined structure. Today, we are becoming more and more aware of the fact that delivery of the active compound to the target site is a key. The present volume gives a topical overview on various modern approaches to drug targeting covering today's options for specific carrier systems allowing successful drug treatment at various sites of the body difficult to address and allowing to increase the benefit-risk-ratio to the optimum possible.

Autoren/Hrsg.

Schäfer-Korting, Monika

Inhaltsverzeichnis

1;Preface;5
2;Contents;8
3;Part I Fundamentals;14
3.1;Passive and Active Drug Targeting: Drug Delivery to Tumors as an Example;15
3.1.1;Drug Targeting: General Considerations;16
3.1.2;Concepts of Passive and Active Targeting;18
3.1.3;Pharmaceutical Carriers: Liposomes and Micelles as Examples;22
3.1.4;Chemistry Used to Provide Pharmaceutical Nanocarriers with Various Functions;27
3.1.5;Longevity of Nanocarriers in the Blood and its Importance for Drug Delivery;29
3.1.6;Passive Accumulation of Liposomes and Micelles in Tumors;33
3.1.7;Active Tumor Targeting with Drug-Loaded Liposomes;38
3.1.8;Active Tumor Targeting with Drug-Loaded Micelles;45
3.1.9;Conclusion;47
3.1.10;References;48
3.2;Nanoparticle Technologies for Cancer Therapy;66
3.2.1;Introduction;67
3.2.2;Nanoparticle Technologies;70
3.2.2.1;Liposome Nanoparticles;72
3.2.2.2;Polymer-Drug Conjugates Nanoparticles;73
3.2.2.3;Polymeric Nanoparticles;74
3.2.2.4;Micelle Nanoparticles;75
3.2.2.5;Dendrimer Nanoparticles;76
3.2.2.6;Polymersome Nanoparticles;77
3.2.2.7;Protein Nanoparticles;77
3.2.2.8;Biological Nanoparticles;78
3.2.2.9;Inorganic Nanoparticles;78
3.2.2.10;Hybrid Nanoparticles;80
3.2.3;Strategies for Cancer Therapy Using Nanoparticles;81
3.2.3.1;Metastatic Cancer;81
3.2.3.2;Non-Targeted Nanoparticles;82
3.2.3.3;Targeted Nanoparticles;85
3.2.4;Summary;87
3.2.5;References;88
3.3;Biosensing and Drug Delivery at the Microscale;98
3.3.1;Progress and Challenges in Controlled Drug Delivery;99
3.3.2;Polymer Actuator for Controlled Drug Delivery;101
3.3.3;Complex Drug Releasing Systems for Synchronous Drug Delivery;103
3.3.4;A Novel Nanoscale Valve Responding to pH Changes May Allow a Targeted Drug Release;104
3.3.5;pH-Responsive Supramolecular Nano-valves;105
3.3.6;Electronically Controlled ``Smart´´ Pill;106
3.3.7;Novel Micro- and Nano-Mechanical Drug Delivery Implants;108
3.3.8;Highlights in Micro-Machined Biosensing Drug Delivery Devices;111
3.3.9;Novel Technological Challenges in Drug Delivery - Nano-Micro-Implants;114
3.3.10;Novel Aspects of Electronically Controlled Drug Delivery Systems;116
3.3.11;Biosensing of Drug Delivery in In Vitro Tissue Models;118
3.3.12;Biosensing of Drug Delivery In Vivo - Microelectrodes in Endoluminal Sensors;119
3.3.13;References;121
4;Part II Devices;124
4.1;Lipid Nanoparticles: Effect on Bioavailability and Pharmacokinetic Changes;125
4.1.1;Introduction;127
4.1.2;Definition of Lipid Nanoparticles (SLN vs. NLC);128
4.1.2.1;Solid Lipid Nanoparticles (SLN);131
4.1.2.2;Nanostructured Lipid Carriers (NLC);132
4.1.3;Effects of Lipid Polymorphism on API Bioavailability;133
4.1.4;Lipid Nanoparticles Applications;135
4.1.4.1;Oral Delivery;135
4.1.4.2;Pulmonary Delivery;138
4.1.4.3;Parenteral Delivery and Drug Distribution;140
4.1.4.4;Brain Targeting;141
4.1.5;Conclusions and Perspectives;144
4.1.6;References;144
4.2;Viral Vectors for Gene Transfer: Current Status of Gene Therapeutics;152
4.2.1;Gene Therapy: Definition and State of the Art;154
4.2.2;AAV Vectors for Gene Therapy;156
4.2.2.1;Overview of Properties;156
4.2.2.2;AAV Structure;157
4.2.2.3;AAV Life Cycle;157
4.2.2.4;Cell Receptors Used by AAV;158
4.2.2.5;AAV Vector Production;158
4.2.2.5.1;AAV Vector Production by Cotransfection of Packaging Plasmids;158
4.2.2.5.2;Upscaling of AAV Vector Production;159
4.2.2.5.3;AAV Vector Purification;161
4.2.2.5.4;Quantification of AAV Vector Yields;162
4.2.2.6;AAV Vector Persistence and Safety;163
4.2.2.7;AAV Split Vectors;164
4.2.2.8;Dimeric, Self-Complementary (sc) AAV Vectors;164
4.2.2.9;Cell Targeting Strategies for AAV;165
4.2.2.10;Future Directions;166
4.2.3;Retrovirus Vectors for Gene Therapy;166
4.2.3.1;Retrovirus Structure and Life Cycle;167
4.2.3.2;Design and Development of Oncoretroviral Vectors;167
4.2.3.3;Self-Inactivating (SIN) Oncoretroviral Vectors;168
4.2.3.4;Design and Development of Lentiviral Vectors;170
4.2.3.5;Safety of Retrovirus Integration;171
4.2.3.6;Production and Stability of Retroviral Vectors;172
4.2.3.7;Purification and Upscaling of Retroviral Vectors;173
4.2.3.8;Vector Quantitation and Quality Assessment;174
4.2.3.9;Future Directions of Retroviral Vector Development;175
4.2.4;Outlook;176
4.2.5;References;177
4.3;Pulmonary Drug Delivery: Medicines for Inhalation;180
4.3.1;Introduction;182
4.3.2;Principles of Aerosol Delivery;183
4.3.2.1;Inhalation Therapy;183
4.3.2.2;Lung Structure;184
4.3.2.3;Aerosol Deposition;185
4.3.2.4;Lung Clearance;186
4.3.3;Pulmonary Drug Delivery Approaches;188
4.3.3.1;Asthma/COPD;188
4.3.3.2;Immunosuppressives;189
4.3.3.3;Vaccines;190
4.3.3.4;Anti-Infectives;191
4.3.3.5;Pulmonary Gene Therapy;192
4.3.3.6;Lung Cancer Therapy;194
4.3.4;Future Prospects;195
4.3.5;References;196
4.4;Needle-Free Vaccine Injection;202
4.4.1;Introduction;203
4.4.2;Targeting Skin and Mucosal Cells: The Immunological Rationale;204
4.4.3;Engineering of Physical Approaches for the Targeting of Skin and Mucosal Cells;206
4.4.3.1;Mechanical Properties of the SC Barrier;207
4.4.3.2;Biological Approaches;207
4.4.3.3;Physical Cell Targeting Approaches;208
4.4.4;Biolistic Microparticle Delivery;210
4.4.4.1;Biolistics Operating Principle;210
4.4.4.2;Engineering of Hand-Held Biolistic Devices for Clinical Use;211
4.4.4.3;Ballistics Microparticle Delivery to Skin;216
4.4.4.3.1;Theoretical Model for Ballistic Impact into Skin;216
4.4.4.3.2;Locations of Microparticles into Skin;217
4.4.4.3.3;Skin Cell Death from Ballistic Impact;220
4.4.4.4;Clinical Results and Commercial Application;221
4.4.5;Conclusion;224
4.4.6;References;224
4.5;Pharmaceutically Used Polymers: Principles, Structures, and Applications of Pharmaceutical Delivery Systems;229
4.5.1;Introduction;230
4.5.2;Pharmaceutically Used Polymers and Biomaterials;232
4.5.2.1;Classification of Pharmaceutically Used Polymersand Biomaterials - An Overview;233
4.5.2.2;Orally Applied Polymers: Properties and Applications;234
4.5.2.2.1;Starch;234
4.5.2.2.2;Hydroxylpropyl Methylcellulose;239
4.5.2.2.3;Eudragit;240
4.5.2.2.4;Carbopol Polymers;241
4.5.2.2.5;Pluronic Block Copolymers;241
4.5.2.2.6;Alginates;242
4.5.2.3;Systemically Applied Polymers;243
4.5.2.3.1;Poly(lactide-co-glycolide) and Related Polymers;244
4.5.2.3.2;PEG Polymers;244
4.5.2.3.3;Dextran;245
4.5.2.3.4;HPMA Copolymers;245
4.5.2.3.5;Poly(anhydrides);246
4.5.2.4;Current Developments: Dendritic Polymers;247
4.5.3;Specific Aspects of Polymers in Oral Drug Delivery;249
4.5.3.1;Modified Release Dosage Forms;250
4.5.3.2;Gastro-enteric Coatings;251
4.5.3.3;Matrix Systems;251
4.5.3.4;Reservoir Systems;252
4.5.3.5;Osmotic Pump Systems;253
4.5.4;References;255
4.6;Mucoadhesive Drug Delivery Systems;259
4.6.1;Introduction;260
4.6.2;Mucoadhesion;260
4.6.2.1;Mucus;260
4.6.2.2;Mucoadhesion Theories and Binding Types;261
4.6.2.2.1;Chemical Bonds;261
4.6.2.2.2;Theories of Adhesion;261
4.6.2.3;Mucoadhesion Tests;262
4.6.2.3.1;Visual Tests;262
4.6.2.3.2;Tensile Tests;264
4.6.2.3.3;Rheological Tests;264
4.6.2.3.4;In Vivo Methods;264
4.6.2.4;Factors Influencing Mucoadhesion;265
4.6.2.4.1;Polymeric Factors;265
4.6.2.4.2;Environmental Factors;265
4.6.2.4.3;Mucus Physiology;266
4.6.3;Mucoadhesive Polymers and Derivatives;266
4.6.3.1;Anionic Polymers;266
4.6.3.2;Cationic Polymers;266
4.6.3.3;Non-Ionic Polymers;268
4.6.3.4;Amphiphilic Polymers;268
4.6.3.5;Polymer Derivatives;268
4.6.4;Drug Delivery Systems;269
4.6.4.1;Nasal;269
4.6.4.2;Buccal;269
4.6.4.3;Vaginal;270
4.6.4.4;Ocular;270
4.6.4.5;Oral;271
4.6.5;Conclusion;272
4.6.6;References;273
4.7;Intrauterine Drug Delivery for Contraception and Gynaecological Treatment: Novel Approaches;275
4.7.1;Introduction;276
4.7.2;Frameless Intrauterine Devices and Systems;278
4.7.2.1;Development of Frameless Intrauterine Devices and Systems;278
4.7.2.2;Frameless Copper-Releasing Intrauterine Devices;280
4.7.2.2.1;Description;280
4.7.2.2.2;Efficacy;281
4.7.2.2.3;Safety and Side Effects;281
4.7.2.2.4;Insertion, Expulsion and Removal;283
4.7.2.2.5;Perforation;283
4.7.2.2.6;Special Uses of the Frameless Copper IUD;284
4.7.2.2.7;Lifespan;285
4.7.2.3;The Frameless Levonorgestrel Intrauterine System (LNG-IUS);285
4.7.2.4;Description;285
4.7.2.5;Clinical Performance of the Frameless LNG-IUS;286
4.7.2.6;Acceptability and Endometrial Safety of the Frameless LNG-IUS in Women Using Estrogen Replacement Therapy (ERT);287
4.7.2.7;Effect on Menstrual Blood Loss;287
4.7.2.8;Contraceptive Efficacy;288
4.7.2.9;The Effect of the Frameless LNG-IUS in Women Suffering from Primary or Secondary Dysmenorrhea;288
4.7.3;Framed Levonorgestrel-Releasing Intrauterine Systems;289
4.7.3.1;Development;289
4.7.3.2;The Framed Standard Levonorgestrel-Releasing Intrauterine System;290
4.7.3.2.1;Description;290
4.7.3.3;Clinical Performance of the Framed Standard LNG-IUS;291
4.7.3.3.1;Ease and Safety of Insertion and Contraceptive Performance;291
4.7.3.3.2;Retention;291
4.7.3.3.3;Effect on Menstrual Blood Loss;292
4.7.3.3.4;Long-Term Treatment of Non-Atypical and Atypical Endometrial Hyperplasia;293
4.7.3.4;The Framed Slim Levonorgestrel-Releasing Intrauterine System;294
4.7.3.4.1;Clinical Performance of the Framed Slim LNG-IUS;294
4.7.3.4.1.1;Acceptability and Long-Term Endometrial Safety of the Femilis Slim LNG-IUS in Postmenopausal Women Using Estrogen Replace;294
4.7.4;Concluding Remarks;295
4.7.4.1;Long-Acting Contraceptive Methods Should Be Used to Prevent Unintended Pregnancies;295
4.7.4.2;Long-Term Intrauterine Contraceptive Methods to Replace Irreversible Female Sterilization;296
4.7.4.3;Safer Contraception;296
4.7.4.4;Pain Control with Intracervical Anesthesia for IUD/IUS Insertion;297
4.7.4.5;Intrauterine Hormonal, Period-Free, Contraception for All Women;297
4.7.4.6;Intrauterine Hormonal Contraception Can Prevent the Need for Hysterectomy;298
4.7.4.7;Reducing The Risk of Postmenopausal Heart Disease, Stroke, Dementia and Alzheimer disease;299
4.7.4.8;The Future;300
4.7.5;References;301
4.8;Drug-Eluting Medical Implants;307
4.8.1;Drug-Eluting Vascular Stents;308
4.8.1.1;Introduction: Restenosis and Drug-Eluting Stents;308
4.8.1.2;The First Generation of Drug-Eluting Stents (DES-I);309
4.8.1.2.1;Agents;310
4.8.1.2.2;Drug Release Mechanisms;311
4.8.1.2.3;Real World;313
4.8.1.3;The Second Generation of Drug-Eluting Stents (DES-II);316
4.8.1.3.1;Platforms;316
4.8.1.3.2;New Agents;316
4.8.1.3.3;New Drug-Release Mechanisms;317
4.8.1.4;Biodegradable Stents;319
4.8.1.5;Novel Drug-Eluting Highly Porous Stent Coatings;324
4.8.2;Drug-Eluting Wound Dressings;326
4.8.2.1;Introduction: Infection, Wound Dressings and Local Antibiotic Release;326
4.8.2.2;Wound Dressings Based on Synthetic Polymers;328
4.8.2.3;Wound Dressings Based on Natural Polymers;329
4.8.2.4;Composite Fiber Structures Loaded with Antibacterial Drugs for Wound Healing Applications;331
4.8.3;Protein-Eluting Scaffolds for Tissue Regeneration;338
4.8.4;References;340
5;Part III Clinical and Preclinical Applicationof Therapeutics for Systemic Use;350
5.1;Improving Oral Delivery;351
5.1.1;Introduction;352
5.1.1.1;Physicochemical Considerations;354
5.1.1.2;Physiological Conditions in the GI Tract;355
5.1.1.2.1;Oral Cavity and Oesophagus;357
5.1.1.2.2;Stomach;357
5.1.1.2.3;Small Intestine;359
5.1.1.2.4;Large Intestine;361
5.1.2;Formulation Parameters to Improve Oral Delivery;363
5.1.2.1;Size;363
5.1.2.1.1;Effects of Nanosizing;363
5.1.2.1.2;Techniques for the Nanosizing of Drug Particles;365
5.1.2.1.2.1;Bottom-Up Processes;366
5.1.2.1.2.2;Top-Down Processes;367
5.1.2.1.2.3;Wet-Milling;367
5.1.2.1.2.4;High Pressure Homogenisation;368
5.1.2.1.2.4.1;Piston-Gap Homogenisers;368
5.1.2.1.2.4.2;Microfluidisation;369
5.1.2.1.3;Absorption of Nanoparticles;369
5.1.2.2;pH-Dependent Drug Delivery;371
5.1.2.2.1;pH-Sensitive Coatings;372
5.1.2.2.2;pH and Colon Targeting;373
5.1.2.2.3;pH-Responsive Hydrogels;374
5.1.2.3;Swelling;375
5.1.2.4;Osmotic Pressure;378
5.1.2.5;Density;380
5.1.2.6;Enzyme-Mediated Release in the Colon;383
5.1.2.6.1;Prodrugs;384
5.1.2.6.2;Polymeric Coatings and Matrices;384
5.1.2.7;Biorecognition;386
5.1.2.7.1;Targeting to Enterocytes;387
5.1.2.7.2;Targeting to M Cells;387
5.1.2.7.3;Miscellaneous;390
5.1.2.8;Absorption Enhancers;390
5.1.2.8.1;General Considerations;390
5.1.2.8.2;Strategies of Absorption Enhancement;391
5.1.2.8.2.1;Solubilising Excipients;392
5.1.2.8.2.2;The Transcellular Route;393
5.1.2.8.2.3;The Paracellular Route;393
5.1.2.8.2.4;Secretory Transport Inhibitors;394
5.1.2.8.3;Outlook;394
5.1.3;Future Perspectives;395
5.1.4;References;395
5.2;Transdermal Drug Delivery;405
5.2.1;Introduction;406
5.2.2;The Present State of Transdermal Drug Delivery;407
5.2.2.1;Barrier Function of Skin;407
5.2.2.2;Transdermally Delivered Drugs;407
5.2.2.3;Enhancement of Transdermal Drug Delivery;409
5.2.2.4;Local and ``Subcutaneous´´ Drug Delivery;414
5.2.3;Conclusions;414
5.2.4;References;415
5.3;Targeting the Brain - Surmounting or Bypassing the Blood-Brain Barrier;417
5.3.1;Introduction;418
5.3.2;Structure and Function of the Blood-Brain Barrier;418
5.3.3;The Blood-Brain Barrier as a Limiting Factor in the Treatment of CNS Diseases;420
5.3.4;Modulation of Blood-Brain Barrier Function;422
5.3.4.1;Opening of the BBB;423
5.3.4.2;Inhibition of Efflux Transport;424
5.3.4.3;Prevention of Disease-Associated or Therapy-Induced Changes of the Blood-Brain Barrier;426
5.3.5;Bypassing the Blood-Brain Barrier;429
5.3.5.1;Nano-Sized Carrier Systems and Drug Conjugates;429
5.3.5.2;Intranasal Administration;430
5.3.5.3;Intracerebral Administration;430
5.3.6;Conclusions;432
5.3.7;References;432
5.4;Carriers in the Topical Treatment of Skin Disease;439
5.4.1;Introduction;441
5.4.2;(Per-)Cutaneous Absorption;441
5.4.2.1;Skin Morphology and Barrier Function;441
5.4.2.2;Skin Penetration Pathways;443
5.4.2.3;Assessment of (Per-)Cutaneous Absorption;444
5.4.2.4;Enhancement of (Per-)Cutaneous Absorption;445
5.4.3;Drug Carriers - Technological Aspects;446
5.4.3.1;Liposomes;447
5.4.3.2;Niosomes;449
5.4.3.3;Solid Lipid Nanoparticles and Nanostructured Lipid Carriers;449
5.4.3.4;Micro- and Nanoemulsions;450
5.4.3.5;Polymer Particles Including Dendrimers;450
5.4.3.6;Miscellaneous Nanoparticles;451
5.4.4;Current Therapy in the Main Target Indications for API-Loaded Nanoparticulate Delivery Systems;452
5.4.5;Clinical and Preclinical Data of Carrier-Loaded API;453
5.4.5.1;Liposomes and Niosomes;453
5.4.5.2;Lipid Nanoparticles;457
5.4.5.3;Microparticles;461
5.4.5.4;Microemulsions;462
5.4.5.5;Polymer Particles Including Microparticles and Dendrimers;464
5.4.6;Miscellaneous Approaches;465
5.4.7;Conclusion;465
5.4.8;References;465
5.5;Medical Devices for the Treatment of Eye Diseases;473
5.5.1;Introduction;474
5.5.2;Targeted Vitreoretinal Diseases;477
5.5.2.1;Cytomegalovirus (CMV) Retinitis;478
5.5.2.2;Noninfectious Uveitis;479
5.5.2.3;Macular Edema;479
5.5.2.4;Retinitis Pigmentosa;480
5.5.2.5;Age-Related Macular Degeneration (AMD);481
5.5.2.6;Proliferative Vitreoretinopathy (PVR);482
5.5.3;Nonbiodegradable Devices;483
5.5.3.1;Vitrasert: Nonbiodegradable Implant with Ganciclovir;483
5.5.3.2;Retisert: Nonbiodegradable Implant with Fluocinolone Acetonide;485
5.5.3.3;I-vationTM: Nonbiodegradable Implant with Triamcinolone Acetonide;486
5.5.3.4;Medidur: Nonbiodegradable Insert with Fluocinolone Acetonide;486
5.5.4;Biodegradable Devices;487
5.5.4.1;Posurdex: Biodegradable Insert with Dexamethasone;487
5.5.4.2;Injectable Microspheres;488
5.5.5;Triamcinolone Acetonide Crystal Suspensions;488
5.5.6;NT-501: Encapsulated Cell Technology (ECT);489
5.5.7;Conclusion;489
5.5.8;References;490
6;Index;494