Intracellular Delivery

A critical review is attempted to assess the status of nanomedicine entry onto the market. The emergence of new potential therapeutic entities such as DNA and RNA fragments requires that these new “drugs” will need to be delivered in a cell-and organelle-specific manner. Although efforts have been made over the last 50 years or so to develop such delivery technology, no effective and above all clinically approved protocol for cell-specific drug delivery in humans exists as yet. Various particles, macromolecules, liposomes and most recently “nanomaterials” have been said to “show promise” but none of these promises have so far been “reduced” to human clinical practice. The focus of this volume is on cancer indication since the majority of published research relates to this application; within that, we focus on solid tumors (solid malignancies). Our aim is critically to evaluate whether nanomaterials, both non-targeted and targeted to specific cells, could be of therapeutic benefit in clinical practice. The emphasis of this volume will be on pharmacokinetics (PK) and pharmacodynamics (PD) in animal and human studies. Apart from the case of exquisitely specific antibody-based drugs, the development of target-specific drug–carrier delivery systems has not yet been broadly successful at the clinical level. It can be argued that drugs generated using the conventional means of drug development (i.e., relying on facile biodistribution and activity after (preferably) oral administration) are not suitable for a target-specific delivery and would not benefit from such delivery even when a seemingly perfect delivery system is available. Therefore, successful development of site-selective drug delivery systems will need to include not only the development of suitable carriers, but also the development of drug entities that meet the required PK/PD profile.

This book features a special subsection of Nanomedicine, an application of nanotechnology to achieve breakthroughs in healthcare. It exploits the improved and often novel physical, chemical and biological properties of materials only existent at the nanometer scale. As a consequence of small scale, nanosystems in most cases are efficiently uptaken by cells and appear to act at the intracellular level. Nanotechnology has the potential to improve diagnosis, treatment and follow-up of diseases, and includes targeted drug delivery and regenerative medicine; it creates new tools and methods that impact significantly upon existing conservative practices. This volume is a collection of authoritative reviews. In the introductory section we define the field (intracellular delivery). Then, the fundamental routes of nanodelivery devices, cellular uptake, types of delivery devices, particularly in terms of localized cellular delivery, both for small drug molecules, macromolecular drugs and genes; at the academic and applied levels, are covered. The following section is dedicated to enhancing delivery via special targeting motifs followed by the introduction of different types of intracellular nanodelivery devices (e.g. a brief description of their chemistry) and ways of producing these different devices. Finally, we put special emphasis on particular disease states and on other biomedical applications, whilst diagnostic and sensing issues are also included. Intracellular delivery / therapy is a highly topical which will stir great interest. Intracellular delivery enables much more efficient drug delivery since the impact (on different organelles and sites) is intracellular as the drug is not supplied externally within the blood stream. There is great potential for targeted delivery with improved localized delivery and efficacy.

This book elaborates on drug delivery targeting via intracellular delivery, specifically through the Receptor Mediated Endocytosis (RME) approach, due to the involvement of cellular receptors in various grave diseases. Targeted delivery relies on two basic approaches, passive and active targeting. While passive targeting approaches have shown great promise, the improved selectivity achieved with active targeting approaches has resulted in significantly higher efficacy. Interestingly there are numerous strategies for active targeting, many of which are already highlighted in , Targeted Drug Delivery: Concepts and Applications. Nevertheless an exciting and practical strategy for active targeting, which could enable high intracellular delivery, is through exploitation of RME. Cells in the body express receptors to enable various physiological and biochemical processes. As a result, many of these receptors are overexpressed in pathological conditions, or newer receptors expressed due to defective cellular functioning. RME is based on exploitation of such receptors to achieve intracellular delivery. While targeted delivery can have manifold applications, in this book we focus on two major and challenging therapeutic areas; i) Cancer and ii) Infectious Diseases. Targeted Intracellular Drug Delivery by Receptor Medicated Endocytosis discusses the major receptors that are useful for targeted delivery for these afflictions. A major section of this book is dedicated to details regarding their occurrence and location, the recognition domain of the receptor, structure activity relationship of substrate /ligand for selective binding, ligands explored, antagonists for ligand binding and relevance of these aspects for therapy of cancer and infectious diseases. These facets are elucidated with the help of specific examples from academic research and also emphasize commercial products, wherever relevant. In vitro cellular models relied on for assessing receptor mediated cellular targeting and in vivo models depicting clinical efficacy are focused on in a separate section. Finally, we briefly discuss the regulatory and toxicity issues that may be associated specifically with the RME approach of intracellular drug delivery.

This volume is a continuation of Volume 1 following the previously published Editorial. More emphasis is given to novel nanocarrier designs, their characterization and function, and applications for drug discovery and treatment. A number of chapters will deal with nanofibers as a new major application within the biomedical field with a very high success rate particularly in wound healing and diabetic foot and spine injuries. A major new subdivision will deal with mathematical methods for the assembly of nanocarriers both for simulation and function.

This book features a special subsection of Nanomedicine, an application of nanotechnology to achieve breakthroughs in healthcare. It exploits the improved and often novel physical, chemical and biological properties of materials only existent at the nanometer scale. As a consequence of small scale, nanosystems in most cases are efficiently uptaken by cells and appear to act at the intracellular level. Nanotechnology has the potential to improve diagnosis, treatment and follow-up of diseases, and includes targeted drug delivery and regenerative medicine; it creates new tools and methods that impact significantly upon existing conservative practices. This volume is a collection of authoritative reviews. In the introductory section we define the field (intracellular delivery). Then, the fundamental routes of nanodelivery devices, cellular uptake, types of delivery devices, particularly in terms of localized cellular delivery, both for small drug molecules, macromolecular drugs and genes; at the academic and applied levels, are covered. The following section is dedicated to enhancing delivery via special targeting motifs followed by the introduction of different types of intracellular nanodelivery devices (e.g. a brief description of their chemistry) and ways of producing these different devices. Finally, we put special emphasis on particular disease states and on other biomedical applications, whilst diagnostic and sensing issues are also included. Intracellular delivery / therapy is a highly topical which will stir great interest. Intracellular delivery enables much more efficient drug delivery since the impact (on different organelles and sites) is intracellular as the drug is not supplied externally within the blood stream. There is great potential for targeted delivery with improved localized delivery and efficacy.

"This book explores the utility of diverse multifunctional nanocarriers in drug delivery and biomedical applications, especially emphasizing on the synthesis and characterizations of Nano systems along with surface engineering approaches used for active targeting of the drugs. It also includes the recent updates on the applications of the nanocarriers to fulfill the needs of various healthcare system"--

An authoritative and up-to-date survey of the fundamental principles, and practice of drug delivery at the cellular level. On the principles side, the authors discuss the broad spectrum of cellular delivery, ranging from coverage of cell-mediated immunity, gene delivery, and protein targeting, to cellular drug transport, cellular drug permeability, and a variety of carrier system related to targeted drug delivery. On the practice side, the authors focus on technological developments in cellular drug delivery, including novel formulations for the delivery of DNA and antisense oligonucleotides ,as well as drug targeting with immunoglobulin formulations and antibody-mediated approaches.