Intracellular Delivery III: Market Entry Barriers of Nanomedicines (Fundamental Biomedical Technologies (8))

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 2drugs3 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 2nanomaterials3 have been said to 2show promise3 but none of these promises have so far been 2reduced3 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{u2013}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 Front Matter....Pages i-xiii Front Matter....Pages 1-1 Overview of Present Problems Facing Commercialization of Nanomedicines....Pages 3-36 Precision Drugs and Cell-Specific Drug Delivery....Pages 37-46 Front Matter....Pages 47-47 Extracellular Matrix Degrading Enzymes for Nanocarrier-Based Anticancer Therapy....Pages 49-66 Nanocarrier-Based Anticancer Therapies with the Focus on Strategies for Targeting the Tumor Microenvironment....Pages 67-122 Front Matter....Pages 123-123 A New Approach to Decrease the RES Uptake of Nanodrugs by Pre-administration with Intralipid® Resulting in a Reduction of Toxic Side Effects....Pages 125-146 Front Matter....Pages 147-147 Authentic Vascular and Stromal Structure in Animal Disease Model for Nanomedicine....Pages 149-160 Front Matter....Pages 161-161 Ligand-targeted Particulate Nanomedicines Undergoing Clinical Evaluation: Current Status....Pages 163-200 Anti-angiogenic Therapy by Targeting the Tumor Vasculature with Liposomes....Pages 201-228 Accessing Mitochondrial Targets Using NanoCargos....Pages 229-254 Redox-Responsive Nano-Delivery Systems for Cancer Therapy....Pages 255-269 Front Matter....Pages 271-271 Nano-emulsions for Drug Delivery and Biomedical Imaging....Pages 273-300 The Tumor Microenvironment in Nanoparticle Delivery and the Role of Imaging to Navigate Roadblocks and Pathways....Pages 301-322 Microscopic Mass Spectrometry for the Precise Design of Drug Delivery Systems....Pages 323-337 Front Matter....Pages 339-339 Pharmacokinetics and Pharmacodynamics of Nano-Drug Delivery Systems....Pages 341-362 PBPK Modelling of Intracellular Drug Delivery Through Active and Passive Transport Processes....Pages 363-374 Exploiting Nanocarriers for Combination Cancer Therapy....Pages 375-402 Front Matter....Pages 403-403 The Commercialization of Medical Nanotechnology for Medical Applications....Pages 405-449 Back Matter....Pages 451-453 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 highlytopical 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 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 existing conservative practices. This volume is a collection of authoritative reviews. In the introductory part we define the field (intracellular delivery). Then, we first we cover 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; all at academic and applied levels. Following is dedicated to enhancing delivery via special targeting motifs. Second, we introduce different types of intracellular nanodelivery devices (their chemistry, although the coverage is far from complete) and ways of producing these different devices. Third, we put special emphasis on particular disease states and on other biomedical applications. Diagnostic and sensing is also included. The intracellular delivery/therapy is a very pregnant topic 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 a great potential for targeted delivery with improved localized delivery and efficacy 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.