Ways To Improve Tumor Uptake And Penetration Of Drugs Into Solid Tumors
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Ways to improve tumor uptake and penetration of drugs into solid tumors
Author: Fabrizio Marcucci
language: en
Publisher: Frontiers E-books
Release Date: 2014-12-05
The main scope of this topic is to give an update on pharmacologic and non-pharmacologic approaches to enhance uptake and penetration of cancer drugs into tumors. Inadequate accumulation of drugs in tumors has emerged over the last decade as one of the main problems underlying therapeutic failure and drug resistance in the treatment of cancer. Insufficient drug uptake and penetration is causally related to the abnormal tumor architecture. Thus, poor vascularization, increased resistance to blood flow and impaired blood supply represent a first obstacle to the delivery of antitumor drugs to tumor tissue. Decreased or even inverted transvascular pressure gradients compromise convective delivery of drugs. Eventually, an abnormal extracellular matrix offers increased frictional resistance to tumor drug penetration. Abnormal tumor architecture also changes the biology of tumor cells, which contributes to drug resistance through several different mechanisms. The variability in vessel location and structure can make many areas of the tumor hypoxic, which causes the tumor cells to become quiescent and thereby resistant to many antitumor drugs. In addition, the abnormally long distance of part of the tumor cell population from blood vessels provides a challenge to delivering cancer drugs to these cells. We have recently proposed additional mechanisms of tumor drug resistance, which are also related to abnormal tumor architecture. First, increased interstitial fluid pressure can by itself induce drug resistance through the induction of resistance-promoting paracrine factors. Second, the interaction of drug molecules with vessel- proximal tumor cell layers may also induce the release of these factors, which can spread throughout the cancer, and induce drug resistance in tumor cells distant from blood vessels. As can be seen, abnormal tumor architecture, inadequate drug accumulation and tumor drug resistance are tightly linked phenomena, suggesting the need to normalize the tumor architecture, including blood vessels, and/or increase the accumulation of cancer drugs in tumors in order to increase therapeutic effects. Indeed, several classes of drugs (that we refer to as promoter drugs) have been described, that promote tumor uptake and penetration of antitumor drugs, including those that are vasoactive, modify the barrier function of tumor vessels, debulk tumor cells, and overcome intercellular and stromal barriers. In addition, also non-pharmacologic approaches have been described that enhance tumor accumulation of effector drugs (e.g. convection-enhanced delivery, hyperthermia, etc.). Some drugs that have already received regulatory approval (e.g. the anti-VEGF antibody bevacizumab) exert antitumor effects at least in part through normalization of the tumor vasculature and enhancement of the accumulation of effector drugs. Other drugs, acting through different mechanisms of action, are now in clinical development (e.g. NGR-TNF in phase II/III studies) and others are about to enter clinical investigation (e.g. JO-1).
Lab-on-a-chip Devices for Advanced Biomedicines
Author: Arpana Parihar
language: en
Publisher: Royal Society of Chemistry
Release Date: 2024-08-14
The global miniature devices market is poised to surpass a valuation of $12–$15 billion USD by the year 2030. Lab-on-a-chip (LOC) devices are a vital component of this market. Comprising a network of microchannels, electrical circuits, sensors, and electrodes, LOC is a miniaturized integrated device platform used to streamline day-to-day laboratory functions, run cost-effective clinical analyses and curb the need for centralized instrumentation facilities in remote areas. Compact design, portability, ease of operation, low sample volume, short reaction time, and parallel investigation stand as the pivotal factors driving the widespread acceptance of LOC within the biomedical community. In this book, the Editors meticulously explore LOC through three key ‘Ts’: Theories (microfluidics, microarrays, instrumentation, software); Technologies (additive manufacturing, artificial intelligence, computational thinking, smart consumables, scale-up tactics, and biofouling); and Trends (biomedical analysis, point-of-care diagnostics, personalized healthcare, bioactive synthesis, disease diagnosis, and space applications) This comprehensive text not only provides readers with a thorough understanding of the current advancements in the LOC domain but also offers valuable insights to support the utilization of miniaturized devices for enhanced healthcare practices. Aimed at career researchers looking for instruction in the topic and newcomers to the area, the book is also useful for undergraduate and postgraduate students embarking on new studies or for those interested in reading about the LOC platform.
The Textbook of Nanoneuroscience and Nanoneurosurgery
This textbook highlights the exciting field of nanoneuroscience and its potential to transform how we diagnose and treat neurological disorders. "The Textbook of Nanoneuroscience and Nanoneurosurgery," dives deep into this emerging field, exploring the latest tools and techniques currently being developed at the nanoscale level. Key areas of focus include: Nanoplatforms: The book explores how scientists utilize materials on a near-microscopic scale for neurosurgery, neurology, and brain imaging applications. Bridging the Gap: Regulatory hurdles for translating research from the lab to real-world use are addressed, paving the way for future advancements. The Future is Now: The book showcases recent breakthroughs already impacting patient care alongside promising areas with significant potential. Collaboration is Key: Insights from over 220 researchers and 5000+ references, along with illustrative figures in B/W and color, provide a comprehensive overview of this dynamic field. With its focus on minimally invasive procedures and the latest regulatory considerations, "The Textbook of Nanoneuroscience and Nanoneurosurgery" equips researchers and medical professionals with the knowledge to develop groundbreaking treatments for neurological conditions. The text also reviews the latest regulatory guidelines that influence the translation of nanotechnological research from the laboratory to the clinic and the most recent information on biodevices and pharmaceutical spinoffs. It highlights presidential and congressional initiatives and programs that may impact the field soon. Some reviews of the First edition of the textbook. "...a significant contribution to the field of nanoneuroscience and nanoneurosurgery ... the reader will come away with a deeper understanding of the history of nanotechnology and medicine." —Neuroscience "This is a monumental first textbook on nanoneurosurgery. ... recommended reading for neurosurgeons, neurologists, neuroradiologists, and neuroscientists involved in research on new techniques for application in neurosurgery. Biomedical engineers and various companies developing instruments and devices would benefit from the wealth of information about trends for the development of new technologies for neurosurgery." K. K. Jain, MD, Basel, Switzerland "Phenomenal body of knowledge in this book that would take eons to collate by myself. Every answer to every one of my questions plus heaps more. Essential reading for everyone interested in the field. A must-have!" Albert Deme "This is an amazing foray into the future of a largely unexplored, but increasingly critical medical domain.....I have learned much from every page of this captivating text, and I highly recommend it to any medical student, researcher, medical professional in the neurosciences, or anyone who has an interest in the human brain and the future of medicine, to gather a glimpse of the incredible and beneficial paradigm shifts that will soon impact the field of neuroscience." Frank Boehm, British Columbia, Canada