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Pharmaceutical Nanotechnology: Innovation and Production, 2 Volumes

Pharmaceutical Nanotechnology: Innovation and Production, 2 Volumes

Jean Cornier (Editor), Andrew Owen (Editor), Arno Kwade (Editor), Marcel Van de Voorde (Editor)

ISBN: 978-3-527-80069-8

Nov 2016

775 pages

$268.99

Description

With its focus on concrete methods and recent advances in applying nanotechnology to develop new drug therapies and medical diagnostics, this book provides an overall picture of the field, from the fundamentals of nanopharmacy with the characterisation and manufacturing methods to the role of nanoparticles and substances. Actual examples of utilization include drug development issues, translation to the clinic, market prospects, and industrial commercialization aspects. The applications described are taken from cancer treatment as well as other major therapeutic areas, such as infectious diseases and dermatology. An in-depth discussion on safety, regulatory, and societal aspects rounds off the book.
Written by a top team of editors and authors composed of the leading experts in Europe and the USA who have pioneered the field of nanopharmacy!

Foreword XXVII

Industrial Requirement on Nanopharmacy Research XXIX

Introduction XXXI

Volume 1

Part One Entry to the Nanopharmacy Revolution 1

1 History: Potential, Challenges, and Future Development in Nanopharmaceutical Research and Industry 3
Albertina Ariën and Paul Stoffels

1.1 Nanopharmaceuticals in Cancer Therapy 4

1.2 Nanoparticles Actively Using the Host Machinery 5

1.3 Nanopharmaceuticals for Oral Administration and Long-Acting Injectable Therapy 8

1.4 Bridging Future Nanomedicines to Commercialization 10

1.5 Future Outlook 11

Acknowledgments 12

References 12

2 Nanoscale Drugs: A Key to Revolutionary Progress in Pharmacy and Healthcare 17
Simon Sebastian Raesch, Marina Poettler, Christoph Alexiou, and Claus-Michael Lehr

2.1 Introduction 17

2.2 Nanopharmacy Concepts to Improve the Safety and Efficacy of Medicines 20

2.3 Technical Realization of Nanopharmaceuticals 30

2.4 Safety of Nanopharmaceuticals 34

2.5 Present and Future of Nanopharmacy 35

References 37

3 The Emergence of Nanopharmacy: From Biology to Nanotechnology and Drug Molecules to Nanodrugs 43
Marilena Hadjidemetriou, Zahraa Al-Ahmady, Mariarosa Mazza, and Kostas Kostarelos

3.1 Introduction 43

3.2 First Generation of Nanopharmaceuticals: From Drug Molecules to Nanodrugs 45

3.3 Conclusion 55

References 56

4 Understanding and Characterizing Functional Properties of Nanoparticles 63
Ester Polo, Valentina Castagnola, and Kenneth A. Dawson

4.1 Introduction 63

4.2 The Approach to Characterization 70

References 77

5 Omics-Based Nanopharmacy: Powerful Tools Toward Precision Medicine 81
Daniel Rosenblum and Dan Peer

5.1 Introduction 81

5.2 Precision Medicine 82

5.3 “OMICS” – New Era in Understanding Pathology 86

5.4 Nanomedicine 90

5.5 Future Outlook 93

Acknowledgments 96

References 96

Part Two Fundamentals of Nanotechnology in Pharmacy 101

6 Nanostructures in Drug Delivery 103
Salma Nabil Tammam and Alf Lamprecht

6.1 Introduction 103

6.2 Nanocarrier Classification 103

6.2.1 Inorganic Nanostructures 104

6.3 Drug Loading and Release 116

6.4 General Discussion and Conclusions 123

References 124

7 Characterization Methods: Physical and Chemical Characterization Techniques 135
Sven Even F. Borgos

7.1 The Need for Nanomedicine-Specific Characterization 135

7.2 The Assay Cascade: From Basic Properties to Complex Interactions 136

7.3 Physicochemical Characterization of Pristine Nanoparticles 137

7.4 Characterization of Nanoparticles in the Biological Environment 144

7.5 Conclusions and Future Outlook 149

References 150

8 Nanoparticle Characterization Methods: Applications of Synchrotron and Neutron Radiation 157
Martha Brennich, Marité Cardenas, Hiram Castillo-Michel, Marine Cotte, V. Trevor Forsyth, Michael Haertlein, Simon A. J. Kimber, Geraldine Le Duc, Edward P. Mitchell, Adam Round, Murielle Salome, and Michael Sztucki

8.1 Advanced Characterization: Synchrotron Light and Neutron Sources 157

8.2 Application Examples 159

8.3 Going Beyond Characterization Using Synchrotron X-rays: Nanoparticles for Diagnostic and Therapeutic pproaches 168

8.4 Looking Ahead and Conclusions 169

Acknowledgments 170

References 171

9 Overview of Techniques and Description of Established Processes 175
Jan Henrik Finke, Michael Juhnke, Arno Kwade, and Heike Bunjes

9.1 Introduction 175

9.2 Processing of Liquid Drug Carrier Formulations 176

9.3 Drug Nanoparticles and Process Chains to Solid Formulations 192

9.4 Industrial Status and Framework 215

9.5 Perspectives for Academia, Industry, and Regulatory Authorities 216

References 217

10 Nanopharmacy: Exploratory Methods for Polymeric Materials 231
Kuldeep Bansal, Luana Sasso, Hiteshri Makwana, Sahar Awwad, Steve Brocchini, and Cameron Alexander

10.1 Introduction 231

10.2 Rationale for the Use of Polymers in Nanomedicines 232

10.3 Polymer Structures and Properties 234

10.4 Formulation of Copolymers into Micelles, Vesicles, and Nanoparticles 236

10.5 Conjugation of Polymers to Drugs and Proteins 240

10.6 Recent Advances in Polymer Synthesis for Therapeutic Applications 248

10.7 Controlled Radical Polymerization (CRP) 259

10.8 Concluding Remarks 260

References 261

11 Overview and Presentation of Exploratory Methods for Manufacturing Nanoparticles/“Inorganic Materials” 271
Xavier Le Guevel

11.1 Introduction 271

11.2 Gold NPs 272

11.3 Magnetic NPs 279

11.4 Metal Oxide NPs 282

11.5 Others (Silver, Quantum Dots, and Lanthanides) 284

11.6 Conclusion and Perspective 285

Acknowledgment 285

References 285

12 Scale-Up and cGMP Manufacturing of Nanodrug Delivery Systems for Clinical Investigations 295
Mostafa Nakach and Jean-René Authelin

12.1 Introduction 295

12.2 Presentation of Major Manufacturing Processes of Different Nanodrug Delivery Systems 296

12.3 Nanodrug Delivery Systems as Marketed Products 302

12.4 Particle/Vesicle Size Reduction Technologies 302

12.5 Process Development and Scale-Down/Scale-Up Strategy 308

12.6 Technological Concept for Manufacture of Drug Product for Human Use (GMP Unit) 322

12.7 Conclusion 327

References 327

13 Occupational Safety and Health 331
Thomas H. Brock

13.1 Nanomaterials at the Workplace 331

13.2 Legal Aspects 335

13.3 Management of Uncertainty 336

13.4 Risks of Nanomaterials for Researchers and Workers 336

13.5 Prudent Practices and Proven Concepts for Controlling Risks 338

13.6 Instruction and Training 351

13.7 Summary 352

References 352

Volume 2

Part Three Development of Nanopharmaceuticals 355

14 Micro- and Nano-Tools in Drug Discovery 357
Andreas Dietzel, Monika Leester-Schädel, and Stephan Reichl

14.1 Introduction 357

14.2 General Concepts of Miniaturization 357

14.3 Micro- and Nanofabrication 359

14.4 Nanoformulation 367

14.5 Organ-on-a-Chip 372

References 375

15 Computational Predictive Models for Nanomedicine 379
Marco Siccardi, Alessandro Schipani, and Andrew Owen

15.1 Introduction 379

15.2 Molecular Modeling in Nanomedicine 381

15.3 Computational Approaches for Predicting Nanotoxicology 384

15.4 Simulation of Nanoparticle Pharmacokinetics 386

15.5 Conclusion 395

References 397

16 Drug Targeting in Nanomedicine and Nanopharmacy: A Systems Approach 403
Jingwei Shao, Lisa McConnachie, and Rodney J.Y. Ho

16.1 Introduction 403

16.2 A Systems Approach to Drug Delivery and Drug Targeting 405

16.3 Current Nanomedicine Products 407

16.4 Transformation of a Discovery of Disease Target to a Therapeutic Product 410

16.5 The Role of Targeted Nanoformulations and a Systems Approach in Drug Development 412

16.6 Targeting Drugs to Sites of Action 413

16.7 A Size-Dependent Targeting to Tissues and Cells 414

16.8 Ligand–Receptor-Based Targeting: Active Drug Targeting 417

16.9 Conclusions and Future Prospects 421

References 422

17 Nanoparticle Toxicity: General Overview and Insights Into Immunological Compatibility 425
Marina A. Dobrovolskaia

17.1 Introduction 425

17.2 Systemic Toxicity 427

17.3 Pulmonary Toxicity 428

17.4 Cutaneous Toxicity 431

17.5 Immunotoxicity 432

17.6 Unintended Presence of Nanosized Materials in Pharmaceutical Formulations 434

17.7 Conclusion 435

Acknowledgments 435

References 436

18 An Overview of Nanoparticle Biocompatibility for Their Use in Nanomedicine 443
Matthew S.P. Boyles, Leagh G. Powell, Ali Kermanizadeh, Helinor J. Johnston, Barbara Rothen-Rutishauser, Vicki Stone, and Martin J.D. Clift

18.1 Introduction 443

18.2 Nanomedicine 444

18.3 Biocompatibility of Nanoparticles for Medical Application 445

18.4 Summary 458

References 459

19 Translation to the Clinic: Preclinical and Clinical Pharmacology Studies of Nanoparticles – The Translational Challenge 469
Rachel Tyson, Leah Osae, Andrew J. Madden, and Andrew T. Lucas, and William C. Zamboni

19.1 Introduction 469

19.2 Nanoparticle Formulations 469

19.3 Pharmacokinetic Characterization 470

19.4 Mononuclear Phagocyte System 470

19.5 Delivery of CMA in Tumor 472

19.6 Methods to Target Brain Tumors 475

19.7 Physical Characteristics 477

19.8 The Effect of MPS on CMA PK and PD 480

19.9 Age 483

19.10 Gender 486

19.11 Tissue and Organ Effects 487

19.12 Drug–Drug Interactions 488

19.13 Prior Treatment 489

19.14 Translational Challenges 490

19.15 Future Perspectives on PK and PD 491

References 492

20 Regulatory Issues in Nanomedicines 497
Marisa Papaluca, Falk Ehmann, Ruben Pita, and Dolores Hernan

20.1 Nanomedicines and the Pharmaceuticals Regulatory Framework in Europe 497

20.2 The European Medicines Agency and Nanomedicines 499

20.3 Is It Important to Define Nanomedicines? 501

20.4 Communicating About Nanomedicines 503

20.5 Liposomal Formulations: State of Play at the EMA 504

20.6 Nanosimilar Colloidal Intravenous Iron-Based Preparations 511

20.7 International Landscape and Convergence on Nanomedicines 514

20.8 Conclusions and Way Forward 517

References 518

21 Social Studies of Nanopharmaceutical Research 521
Michael Schillmeier

21.1 Engaging with Ethical, Legal, and Social Implications of Nanoresearch 521

21.2 Nanopharmacy and the “Culture of Promise” 522

21.3 From “Science Meets Society” to Translation as a Social Process 523

21.4 Metaphors and Nanopharmacy 525

21.5 Nanopharmacy and “Personalized Medicine” 526

21.6 Concluding Remarks 528

References 529

Part Four Pharmaceutical Applications of Nanomaterials 533

22 Nanoparticles for Imaging and Imaging Nanoparticles: State of the Art and Current Prospects 535
Thomas Maldiney and Nathalie Mignet

22.1 Introduction 535

22.2 Conception of Nanotechnologies for Imaging 536

22.3 In Vivo Nanoparticle Imaging to Gain Insight into Nanomedicine Biodistribution and Stability 544

22.4 Translational Interest of Nanoparticles for Medical Imaging 548

22.5 Conclusion 553

References 553

23 Nanoparticle-Based Physical Methods for Medical Treatments 561
Christine Ménager

23.1 Photothermal Therapy 561

23.2 Photodynamic Therapy 565

23.3 Magnetic Hyperthermia 567

23.4 Radiotherapy 571

23.5 Sonodynamic Therapy 572

23.6 Cryosurgery 573

23.7 Future Perspectives 574

References 575

24 Nanodrugs in Medicine and Healthcare: Oral Delivery 579
Alejandro Sosnik

24.1 General Aspects and Challenges of Oral Drug Delivery 579

24.2 Pure Drug Micronization as a Conceptual Preamble to More Complex Drug Delivery 580

24.3 Nanotechnology Platforms for Improved Oral Drug Delivery 581

24.4 Conclusive Remarks 591

Acknowledgments 591

References 591

25 Steroidal Nanodrugs Based on Pegylated Nanoliposomes Remote Loaded with Amphipathic Weak Acids Steroid Prodrugs as Anti-Inflammatory Agents 603
Keren Turjeman and Yechezkel Barenholz

25.1 A Short Relevant Background on Inflammatory and Autoimmune Diseases 603

25.2 Drug Delivery Systems (DDS) Based on Nanoparticles (NP) for the Treatment of Diseases That Involve Inflammation 605

25.3 Glucocorticosteroid as Anti-Inflammatory Agents 607

25.4 Steroidal Nanodrugs Based on Pegylated Nanoliposomes Remote Loaded with Amphipathic Weak Acids Steroid Prodrugs as Anti-Inflammatory Agents 609

25.5 Methods for Loading Drugs into Liposomes 610

25.6 Comparing Various Approaches Used for Formulating Liposomal GCs 612

25.7 The Use of Liposomes Loaded with Steroids as Anti-Inflammatory Agents: A Brief Historical Perspective 615

25.8 Lessons Learned from Experimental Animal Models of Diseases That Involve Inflammation 618

References 625

26 Nanodrugs in Medicine and Healthcare: Pulmonary, Nasal and Ophthalmic Routes, and Vaccination 633
Christel C. Müller-Goymann and Mukta Paranjpe

26.1 Introduction 633

26.2 Different Routes of Administration 634

26.3 Different Types of Nanoparticles for Different Routes of Administration 638

26.4 Manufacturing Processes of Nanoparticles 638

26.5 Different Diseases Targeted Via Nanoparticle-Based Drug Delivery Systems 640

26.6 Challenges Faced in Formulation Development of Nanoparticle-Based Systems 641

References 642

27 Neurodegenerative Diseases – Alzheimer’s Disease 649
Maria Gregori and Francesca Re

27.1 Introduction 649

27.2 Diagnosis 650

27.3 Therapy of Alzheimer’s Disease 653

References 656

Part Five The Nanopharmaceutical Market 661

28 A Practical Guide to Translating Nanomedical Products 663
Raj Bawa

28.1 From the Laboratory to the Clinic: Overcoming the Valley of Death 666

28.2 Irreproducible Preclinical Research: A Bottleneck for Translation? 673

28.3 Protecting Inventions via Patents: The Cornerstone of Translation 678

28.4 Terminology and Nomenclature: Lost in Translation 680

28.5 Gaps in Regulatory Guidance 682

28.6 Conclusions and Outlook 683

28.7 Disclosures and Conflict of Interest 694

References 694

29 Development and Commercialization of Nanocarrier-Based Drug Products 697
Marianne Ashford

29.1 Drivers for New Medicines 697

29.2 Current Marketed Nanomedicines 699

29.3 Developing Nanomedicines 705

29.4 Commercialization of Nanomedicines 722

29.5 Conclusions 732

References 732

30 Future Outlook of Nanopharmacy: Challenges and Opportunities 735
Dan Peer and Marcel Van de Voorde

30.1 Matching the NC’s Delivery Mode of Action (MoA) to the Tumor Type 736

30.2 Nonpredictive Animal Models 737

30.3 The Lack of Reliable Techniques that can Efficiently Characterize NCs and Measure their Stability in the Human Body 737

30.4 The Challenge of Scaling Up NCs 738

References 740

Index 743