The Road from Nanomedicine to Precision Medicine

Shaker A. Mousa, Raj Bawa, Gerald F. Audette, Shaker A. Mousa, Raj Bawa, Gerald F. Audette

• Publisher: Jenny Stanford Publishing
• Year: 2019
• ISBN:
  9781000021271
• Edition: 1
• Topic: Medicine
• Subtopic: Biotechnology in Medicine

The enormous advances in nanomedicine and precision medicine in the past two decades necessitated this comprehensive reference, which can be relied upon by researchers, clinicians, pharmaceutical scientists, regulators, policymakers, and lawyers alike. This standalone, full-color resource broadly surveys innovative technologies and advances pertaining to nanomedicine and precision medicine. In addition, it addresses often-neglected yet crucial areas such as translational medicine, intellectual property law, ethics, policy, FDA regulatory issues, nano-nomenclature, and artificial nano-machines—all accomplished in a user-friendly, broad yet interconnected format. The book is essential reading for the novice and the expert alike in diverse fields such as medicine, law, pharmacy, genomics, biomedical sciences, ethics, and regulatory science. The book's multidisciplinary approach will attract a global audience and serve as a valuable reference resource for industry, academia, and government.

Chapter 1

Drug Delivery at the Nanoscale: A Guide for Scientists, Physicians and Lawyers

Raj Bawa, MS, PhD

Patent Law Department, Bawa Biotech LLC, Ashburn, Virginia, USA

The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York, USA

Guanine Inc., Rensselaer, New York, USA

Copyright © 2020 Raj Bawa. All rights reserved. As a service to authors and researchers, the copyright holder permits unrestricted use, distribution, online posting and reproduction of this article or unaltered excerpts therefrom, in any medium, provided the author and original source are clearly identified and properly credited. The figures and tables in this chapter that are copyrighted to the author may similarly be used, distributed, or reproduced in any medium, provided the author and the original source are clearly identified and properly credited. A copy of the publication or posting must be provided via email to the copyright holder for archival.

Keywords: nanotechnology, nanoscience, nanomedicine, nanotech, nanopharmaceutical, nanodrug, nanomaterial, modern nanotechnology, commercialization, technology transfer, research and development (R&D), over-the-counter (OTC), US Food and Drug Administration (FDA), European Medicines Agency (EMA), National Science Foundation (NSF), nomenclature, regulatory definition, drug delivery, engineered nanotherapeutics, site-specific delivery, theranostics, theranostic drug delivery, nanopotential, nanoscale, nanometer (nm), nanocharacter, nanodimensions, specific surface area (SSA), controlled manipulation, nanoparticles (NPs), Theranos, nanoscale titanium dioxide, silver nanoparticles, Doxil^®, Abbreviated New Drug Application (ANDA), scanning tunneling microscope (STM), transmission electron microscope (TEM), atomic force microscope (AFM), molecular nanotechnology (MNT), International Organization for Standardization (ISO), personalized medicine, precision medicine, genomic medicine, National Nanotechnology Initiative (NNI), efficacy, bioavailability, toxicity, combination products, new molecular entities (NMEs), New Drug Applications (NDAs), new biological entities (NBEs), Biologics License Applications (BLAs), Federal Food, Drug, and Cosmetic Act (FD&C Act), Public Health Service (PHS) Act, drug, biologic, device, Bayh–Dole Act of 1980, Hatch–Waxman Act of 1984, biosimilars, Biologics Price Competition and Innovation Act of 2009 (BPCI Act or Biosimilar’s Act), Humulin^®, monoclonal antibody (mAb), multivalence, NanoCrystal^® technology, nanoscale drug delivery systems (NDDS), drug delivery system (DDS), bioperformance, polyethylene glycol (PEG), Generally Recognized As Safe (GRAS), therapeutic monoclonal antibodies (TMAbs), active pharmaceutical ingredient (API), antibody–drug conjugates (ADCs), the “Magic Bullet” Concept, targeting ligands, liposomes, enhanced permeability and retention (EPR), AmBisome^®, Abraxane^®, Copaxone^®, nonbiologic complex drug (NBCD), nanosimilars, US Government Accountability Office (GAO), Lipodox^®, clinical studies, institutional corruption, “draft” guidance documents, adverse drug reactions (ADRs), nano-combination products (NCPs), Intellectual property (IP), US Patent and Trademark Office (PTO), patents, patent proliferation, product-line-extension, patent agent, patent attorney, patent examiner, Freedom-to-Operate (FTO), nanopatent land grabs, patent thickets, carbon nanotube (CNT), translational medicine (TM), bench-to-bedside, C activation-related pseudoallergy (CARPA), adsorption, distribution, metabolism, and excretion (ADME), Biopharmaceutical Classification Scheme (BCS), Technology Transfer Offices (TTOs), licensing, irreproducibility of preclinical research, Good Clinical Practice (GCP), Good Manufacturing Practice (GMP), Good Laboratory Practice (GLP), physiologically based pharmacokinetic (PBPK) modeling, pharmacokinetics (PK), physicochemical characterization (PCC), institutional review board (IRB), pharmacodynamic (PD) modeling, artificial intelligence (AI), nano-characterization

1.1 Nano Frontiers: An Introduction

Small is beautiful.

—Leopold Kohr (1909–1994), Austrian economist

It has long been an axiom of mine that the little things are infinitely the most important.

—Arthur Coyle Doyle (1859–1930), English author and physician

Great things are done by a series of small things brought together.

—Vincent Van Gogh (1853–1890), Dutch painter

The air is thick with news of nano-breakthroughs. Although “nano” (or nanotech or nanotechnology) is a hot topic for discussion in industry, pharma, patent offices, and regulatory agencies, the average citizen knows very little about what constitutes a nanoproduct, a nanomaterial or a nanodrug. Still, there is no shortage of excitement and hype when it comes to anything nano.¹ Optimists tout nano as an enabling technology, a sort of next industrial revolution that could enhance the wealth and health of nations. They promise that in many areas within nanomedicine² (nanoscale drug delivery systems, theranostics, etc.) will soon be a healthcare game-changer by offering patients access to precision medicine. Pessimists, on the other hand, take a more cautionary position, preaching instead a go-slow approach and warning about the lack of enough scientific information on health risks, general failure on the part of regulatory agencies to formulate clearer guidelines and continuous issuance of patents of dubious scope. They highlight that nano is burdened with inflated expectations with few marketed products. The reality may be somewhere between such extremes. Like any emerging technology, the whole picture is yet to emerge…and we are just getting started! Whatever your stance, nano has already permeated virtually every sector of the global economy, with potential applications consistently inching their way into the marketplace. But, is nano the driving force behind a new industrial revolution in the making or simply a repacking of old scientific ideas and terms? Dissecting hope from fact is often difficult.

Nano is the natural continuation of the miniaturization of materials and medical products that have been steadily arriving in the marketplace. It continues to evolve and play a pivotal role in various industry segments, spurring new directions in research, patents, commercialization, translation, and technology transfer. Although not a distinct field or disciple, it is an interdisciplinary area that draws from the interplay among numerous fields, including materials science, medicine, engineering, colloid science, supramolecular and physical chemistry, drug science, biophysics, and many more.

Nano’s potential benefits are frequently overstated or inferred to be very close to application when clear bottlenecks to commercial translation exist. In this regard, start-ups, academia, and industry exaggerate basic research and developments (R&D) as potentially revolutionary advances and claim these early-stage discoveries as confirmation of downstream novel products and applications to come. Such “fake medical news” does great disservice to all stakeholders. It not only pollutes the medical literature but also quashes public support for translational activities. This issue is quite serious and often emanates from eminent academic labs from distinguished universities or from established industry players (Box 1.1).

All of this is happening while hundreds of over-the-counter (OTC) products containing silver and other metallic nanoparticles, nanoscale titanium dioxide, carbon nanotubes, and carbon nanoparticles continue to stream into the marketplace without adequate safety testing, labeling or regulatory review. In fact, a large number of nanomaterials and nanoparticles have been synthesized over the last two decades that could be toxic, yet the Environmental Protection Agency (EPA) and the US Food and Drug Administration (FDA) do not seem to know how to regulate most of them [3]. Obviously, consumers should be cautious about potential exposure but industry workers should even be more concerned.

Box 1.1 Nano: Dreams, Hype, Misinformation, and Reality

We live in a society exquisitely dependent on science and technology, in which hardly anyone knows anything about science and technology.

—Carl Sagan (1934–1996), American cosmologist

The rush to celebrate “eureka” moments in science is overshadowing the research enterprise. Some blame the current pervasive culture that focuses on rewarding eye-catching and positive findings. Others point to an increased emphasis on making provocative statements rather than presenting technical details or reporting basic elements of experimental design. “Fantastical claiming” is nothing new to academia and start-ups where exaggerated basic research developments are often touted as revolutionary and translatable advances. Claims of early-stage discoveries are highlighted as confirmation of downstream novel products and applications to come. Even distinguished professors at reputable universities are guilty of such spin or interpretive bias. In this context, nano’s potential benefits are also often oversta...

Table of contents

• Cover
• Half Title
• Series Page
• Title Page
• Copyright Page
• Dedication
• Cover Image
• American Society For Nanomedicine
• CLINAM
• About the Editors
• Table of Contents
• List of Corresponding Authors
• Preface
• 1. Drug Delivery at the Nanoscale: A Guide for Scientists, Physicians and Lawyers
• 2. What Is Precision Medicine? A Primer on Contemporary Issues and Concerns
• 3. FDA’s Role in Paving the Way for Personalized Medicine
• 4. Multifunctional Gold Nanoparticles in Drug Delivery Systems
• 5. Nanoparticles and Nanoparticulate Drug Delivery Systems: Impact of Size and Structure on Functionality
• 6. Self-Assembling Peptide Amphiphiles as a Versatile Future Nanomedicine Platform
• 7. Pharmaceutical Applications of Water-Soluble Polymers in Nanomedicine and Drug Delivery
• 8. Nanomaterials: Tools, Technology, and Methodology of Nanotechnology-Based Biomedical Systems for Diagnostics and Therapy
• 9. Nanomagnetic Resonance Imaging (Nano-MRI) Gives Personalized Medicine a New Perspective
• 10. Advancing Precision Medicine: Tailoring Personalized Therapies
• 11. Precision Medicine for Alzheimer’s Disease Prevention
• 12. Advanced Porphyrin Nanomaterials for Biological Applications
• 13. Cerium Oxide Nanoparticles as a Novel Reactive Oxygen Modulating Nanodrug
• 14. Artificial Nanomachines and Nanorobotics
• 15. Nanomotors for Nucleic Acid, Protein, Pollutant, and Cell Detection
• 16. Magneto-Responsive Scaffolds for Tissue Engineering Applications
• 17. Anti-Cancer and Anti-Angiogenic Properties of Nano-Diamino-Tetrac, A Thyroid Hormone Derivative
• 18. Proteomic Profiling and Predictive Biomarkers in Neuro-Traumatology and Neuro-Oncology
• 19. Nanomedicine and Personalized Care: Facts and Fiction
• 20. Precision Immuno-Oncology: Prospects of Individualized Immunotherapy for Pancreatic Cancer
• 21. Developing a Case-Based Blended Learning Ecosystem to Optimize Precision Medicine: Reducing Overdiagnosis and Overtreatment
• 22. Views from the FDA: Precision Medicine, Genetic Variant Databases and Companion Diagnostics
• 23. Protein-Based Nanoparticle Materials for Medical Applications
• 24. Nanomedicine and Phage Capsids
• 25. Pharmacogenomics: Ethical, Social, and Public Policy Issues
• 26. From Single Level Analysis to Multi-Omics Integrative Approaches: A Powerful Strategy towards the Precision Oncology
• 27. Harmonizing Outcomes for Genomic Medicine: Comparison of eMERGE Outcomes to ClinGen Outcome/Intervention Pairs
• 28. Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine
• 29. Precision or Personalized Medicine for Cancer Chemotherapy: Is There a Role for Herbal Medicine?
• 30. Personomics: The Missing Link in the Evolution from Precision Medicine to Personalized Medicine
• 31. Stem Cell Banking for Regenerative and Personalized Medicine
• 32. Overview of Ethical Issues in Nanomedicine
• 33. Amphiphilic Nanocarrier Systems for Curcumin Delivery in Neurodegenerative Disorders
• 34. Peptide-Based Drug Delivery Systems: Future Challenges, Perspectives, and Opportunities in Nanomedicine
• 35. Hydrogels and Their Applications in Targeted Drug Delivery
• 36. Emergence of Real World Evidence in Precision Medicine
• Index