Nanobiotherapeutic Based Blood Substitutes

This definitive volume will provide the reader with up to date information and the most recent science of the fast-evolving area of nanobiotherapeutic-based blood substitutes. Long studied, there are recent updates that make their use in patients more promising, and with one product approved for human use, many more in the pipeline. These include 2nd generations and even third generation ones, the later with enhancement of red blood cell functions. In addition, there are carefully written and referenced updates on the recent history and products in the field, complete with pathophysiologic and pharmacologic studies to validate and verify the efficacy and safety of many of these new products.

This volume contains a collection of essays by selected authors who are active in the field of blood substitutes research or closely allied disciplines. These essays were delivered as lectures by the authors at the second annual "Current Issues in Blood Substitute Research and Development - 1995" course sponsored jointly by the Departments of Medicine and Bioengineer ing, University of California, San Diego, the National Institutes of Health (NHLBI), and the U.S. Army on March 30, 31, and April 1, 1995 in San Diego. This course had three goals: to present fundaniental discussions of scientific issues critical to further development of artificial oxygen carriers, to provide academicians a forum to discuss their current research, and to provide the companies involved in developing products the opportunity to update the audience on their progress. The organization owes much to the solicited comments of the attendees of the 1994 course. We would like especially to thank the U.S. Army, particularly through the efforts of COL John Hess, who provided significant funding to make publication of this volume possible. In addition, a number of the participating companies provided additional financial support to offset the costs of the course. These include Alliance Pharmaceutical Corp., Hemosol, Nippon Oil and Fat, Northfield Laboratories, and Ortho Biotech.

Currently, hemoglobin (Hb)-based oxygen carriers (HBOCs) are leading candidates as red blood cell substitutes. In addition, HBOCs are also potential oxygen therapeutics for treatment of patients with critical ischemic conditions due to atherosclerosis, diabetes and other conditions. This book will provide readers a comprehensive review of topics involved in the HBOC development. It focusses on current products and clinical applications as well as on emerging technologies and future prospects.

Blood substitutes are solutions designed for use in patients who need blood transfusions, but for whom whole blood is not available, or is not safe. This interest has intensified in the wake of the AIDS and hepatitis C epidemics. Blood Substitutes describes the rationale, current approaches, clinical efficacy, and design issues for all blood substitutes now in clinical trials. The many summary diagrams and tables help make the book accessible to readers such as surgeons and blood bankers, who have less technical expertise than the biochemists and hematologists who are designing and testing blood substitutes. * Includes chapters necessary to the understanding of blood substitutes, including history, toxicity, physiology, and clinical applications* Presents detailed descriptions of the various products that have been developed and have advanced to clinical trials, and some that are in earlier states of development

Presents an up-to-date treatment of research strategies, clinical and commercial developments, and regulatory and economic issues pertaining to the formulation of effective and safe red blood cell substitutes. The text examines regulatory and socioeconomic aspects of blood substitute products, and global tranfusion practices from the perspective of blood banks and the US Food and Drug Administrations. It also includes the mechanisms of action and consequences of blood substitute administration.

Human blood performs many important functions including defence against disease and transport of biomolecules, but perhaps the most important is to carry oxygen – the fundamental biochemical fuel - and other blood gases around the cardiovascular system. Traditional therapies for the impairment of this function, or the rapid replacement of lost blood, have centred around blood transfusions. However scientists are developing chemicals (oxygen therapeutics, or “blood substitutes”) which have the same oxygen-carrying capability as blood and can be used as replacements for blood transfusion or to treat diseases where oxygen transport is impaired. Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood links the underlying biochemical principles of the field with chemical and biotechnological innovations and pre-clinical development. The first part of the book deals with the chemistry, biochemistry, physiology and toxicity of oxygen, including chapters on hemoglobin reactivity and regulation; the major cellular and physiological control mechanisms of blood flow and oxygen delivery; hemoglobin and myoglobin; nitric oxide and oxygen; and the role of reactive oxygen and nitrogen species in ischemia/reperfusion Injury. The book then discusses medical needs for oxygen supply, including acute traumatic hemorrhage and anemia; diagnosis and treatment of haemorrhages in "non-surgical" patients; management of perioperative bleeding; oxygenation in the preterm neonate; ischemia normobaric and hyperbaric oxygen therapy for ischemic stroke and other neurological conditions; and transfusion therapy in β thalassemia and sickle cell disease Finally “old”and new strategies for oxygen supply are described. These include the political, administrative and logistic issues surrounding transfusion; conscientious objection in patient blood management; causes and consequences of red cell incompatibility; biochemistry of red blood cell storage; proteomic investigations on stored red blood cells; red blood cells from stem cells; the universal red blood cell; allosteric effectors of hemoglobin; hemoglobin-based oxygen carriers; oxygen delivery by natural and artificial oxygen carriers; cross-linked and polymerized hemoglobins as potential blood substitutes; design of novel pegylated hemoglobins as oxygen carrying plasma expanders; hb octamers by introduction of surface cysteines; hemoglobin-vesicles as a cellular type hemoglobin-based oxygen carrier; animal models and oxidative biomarkers to evaluate pre-clinical safety of extracellular hemoglobins; and academia – industry collaboration in blood substitute development. Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood is an essential reference for clinicians, haematologists, medicinal chemists, biochemists, molecular biologists, biotechnologists and blood substitute researchers.

This book contains the selected papers presented at the seventh International Symposium on Blood Substitutes (7th ISBS) held at the International Conference Center of Waseda University in Tokyo on 7-10 September 1997. In keeping with the scientific design of the 7th ISBS Symposium, chapters have been carefully selected and organized to showcase the advancements in recent research. This book includes up-to-date clinical results of leading companies which are manufacturing hemoglobin-based or fluorocarbon-based blood substitutes, and covers issues of hemoglobin toxicity and side effects such as vasoconstriction in more detail using carefully designed in vivo and ex vivo techniques. This book is also a collection of various new types of red cell substitutes such as recombinant Hbs, recombinant albumine-lipidheme complex, modified red blood cells, and perfluorochemicals using material science and molecular engineering.