Controlled drug delivery systems have evolved over the past six decades, from the sustained-release Spansule® technology of the 1950s to the highly sophisticated and targeted drug delivery systems of today. Numerous drug delivery systems (DDS) have been successfully developed for clinical applications over the years, and the demand for innovative technologies continues to grow, driving a variety of new developments in the field. This book describes the fundamental concepts and underlying scientific principles of drug delivery, current applications of drug delivery technologies, and potential future developments in the field. It is intended to serve both as a core textbook and as a valuable reference source for students, researchers, practitioners, and scientists in disciplines including the pharmaceutical and formulation sciences, chemical and biomedical engineering, materials science, medicine and oncology, the health sciences, and natural sciences.
In common with the first edition,* our aim is to provide a single, comprehensive, easy-to-read reference book that covers all aspects of controlled drug delivery. To this end, considerable attention has been paid to the overall layout and contents of the text. Chapter 1 opens with a historical introduction to the field of controlled drug delivery to provide relevant background details for the subsequent chapters.
Section I: Fundamental Issues serves as a comprehensive introduction to the fundamental concepts that underpin drug delivery and targeting. Chapter 2 describes the principles of controlled release, including the various mechanisms, types, and mathematical models of controlled release. Chapter 3 describes various technologies to enhance the water solubility of poorly soluble drugs, which has important implications for lead development in the drug discovery process, as well as for the formulation, bioavailability, and therapeutic efficacy of poorly soluble drugs. An important objective of this book is to provide a thorough understanding of the multitude of highly complex biological barriers to successful drug delivery and targeting that pertain in vivo. For this reason, an entire chapter (Chapter 4) is dedicated to providing a comprehensive overview of the characteristics and properties of the various types of epithelial interfaces in the body of relevance for drug delivery strategies; the factors that influence drug transport across these interfaces are also described.
Section II: Parenteral Routes for Drug Delivery and Targeting opens with a chapter on nano-technology, the engineering and manufacturing of materials at the molecular scale, which offers the potential to revolutionize the drug delivery field. Chapter 5 focuses on the application of nano-technology to drug delivery and targeting, and highlights several areas of opportunity. Various limitations of current drug delivery nanotechnologies are also described, in order to help guide future research; in particular, the anatomical, physiological, and pathological obstacles to the targeting concept are discussed. Chapter 6 describes a variety of long-acting injectables and implant platforms that are currently commercially available or at an advanced stage of development; this chapter also reinforces the general concepts and principles of controlled drug release introduced in Chapters 1 and 2.
Section III: Nonparenteral Routes for Drug Delivery and Targeting describes the major epithelial routes of drug delivery currently under investigation. In keeping with the objective to emphasize an understanding of the biological obstacles for successful drug delivery, each chapter of this section begins with a detailed consideration of the relevant anatomical and physiological barriers pertaining specifically to the route in question, as well as the implications therein to successful drug delivery and targeting via this route. The first epithelial route described is the oral route (Chapter 7), the most common and convenient of the existing administration methods for introducing drugs to the bloodstream. The oral route is discussed with respect to the various mechanisms of controlled release, regional targeting, strategies for improving bioavailability, and the use of vaccines. These same themes recur through the following chapters on the various other epithelial routes, many of which also serve as alternative portals of drug entry to the systemic circulation. The chapters in Section III deliberately follow a common format, in order to ease understanding and facilitate learning, and also to highlight the many similarities that exist between the various epithelial routes, as well as the unique attributes associated with each specific route.
Section IV: Emerging Technologies covers some of the new and exciting possibilities that are emerging as future directions in the field. Chapter 14 describes hydrogels and their applications to drug delivery, including as microfluidic chips, biosensors, and stimuli-sensitive DDS. A variety of sophisticated delivery approaches for overcoming the blood–brain barrier (BBB) are described in Chapter 15, as a means of delivering therapeutics to the central nervous system (CNS). Chapter 16 describes the most promising delivery vehicles emerging for gene therapy, including recent advances such as gene delivery systems that can target intracellular organelles. Chapter 17 provides a comprehensive account of vaccines, as well as the current and emerging vaccine delivery systems used for various routes of vaccination. The newly emerged field of theranostics, which holds great promise for personalized therapy, is described in Chapter 18, while Chapter 19 describes the leverage of techniques from the microelectronics industry to precisely fabricate DDS in the nanometer range and the application of such nanofabricated systems to drug delivery.
Section V: Toward Commercialization is an entirely new section for this edition, which reflects the onward success and progress of drug delivery in the 15 years since the publication of the first edition, as technology moves “from bench to bedside.” Chapter 20 describes the more robust and successful methods currently used in drug discovery, design, and development, with particular emphasis on rationally integrating the drug discovery process with the requirements to optimize successful drug delivery, in order to optimize clinical success. The extensive regulatory development pathway for parenteral nanotechnologies is described in Chapter 21—for those working in the preclinical sector, it offers a comprehensive account of the regulatory hurdles that lie ahead. Chapter 22 provides a thorough analysis of the global drug delivery market and market forces, including the latest trends and developments. Chapter 23 presents an engaging account of the clinical translation of a liposomal product (ThermoDox®, a thermal-sensitive liposome for cancer therapy). It provides an illuminating insight, from the inventor’s perspective, into the process—and difficulties—of guiding a DDS through initial funding, development, and preclinical and clinical trials.
In the conclusions of Chapter 24, we discuss some of the future directions for drug delivery and targeting, raise some of the challenges that need to be addressed, and propose some possible solutions and ways forward for research.
In keeping with our aim to produce an accessible, easily comprehensible book, we have endeavored to ensure that the text is clear, concise, and direct. Careful editing has ensured that the final text displays an overall continuity and integrated style. The book is characterized by the ample usage of carefully chosen figures, illustrations, and graphics. Many of the figures have been specially commissioned and are unique and original in the field. Collectively, the artwork greatly assists the clarity and visual appeal of the book, aids understanding, and facilitates our pedagogic, explanatory approach.
We welcome readers’ suggestions, comments, and corrections on the text. Finally, we hope that you enjoy reading this book as much as we enjoyed editing it!
Anya M. Hillery
Kinam Park
* Hillery, A.M., A.W. Lloyd, and J. Swarbrick. 2001. Drug Delivery and Targeting: For Pharmacists and Pharmaceutical Scientists. Boca Raton, FL: CRC Press.