The Use of Resealed Erythrocytes as Carriers and Bioreactors

Until recently the only biomedical use of erythrocytes was in transfusion medicine to restore a normal oxygen delivery. The development of a technology that permits one to open and reseal erythrocytes has dramatically changed this perspective. Currently, a number of teams have shown that engineered erythrocytes can behave as circulating bioreactors for the degradation of toxic metabolites or the inactivation of xenobiotics, as drug delivery systems, as carriers of antigens of vaccinal interest, and in many others biomedical applications. The technology of opening and resealing the erythrocytes has also been used successfully to investigate several basic aspects of erythrocyte metabolism, survival, pathology, etc. Thus, researchers in this field have an extraordinary opportunity to specifically modify the erythrocytes by the introduction of enzymes that generate new metabolic abilities, antibodies that inactivate single metabolic steps, or metabolites that can influence oxygen delivery and/or other cell properties. Furthermore, the pharmacokinetics of any drug can be potentially manipulated by using the erythrocytes as a delivery system. This book, The Use of Resealed Erythrocytes, is based on the fourth meeting of the "International Society for the Use of Resealed Erythrocytes as Carriers and Bioreactors" (I. S. U. R. E. ), held in Urbino, Italy, in 1991, and examines the most recent applications and developments of this technology.

Proceedings of the Fourth International Meeting of the International Society for the Use of Resealed Erythrocytes as Carriers and Bioreactors held in Urbino, Italy, September 5-7, 199

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On Red Blood Cells, Hemolysis and Resealed Ghosts.- Methods and Procedures for Preparing Resealed Erythrocytes.- IHP Entrapment into Human Erythrocytes: Comparison Between Hypotonic Dialysis and DMSO Osmotic Pulse.- Density Gradient Separation of Inositol Hexaphosphate Loaded Red Blood Cells in Various Preparation Conditions.- Quantitative IHP Determination by 31P-NMR: Proposal for a Standardized Protocol.- Determination of Inositol Hexaphosphate (IHP) in Human IHP-Loaded Red Blood Cells by a Simple High Performance Liquid Chromatography Method.- Determination of Purity of Commercially Available Inositol Hexaphosphate (Phytates) and Preparation of a Reference Material.- Standardization of an Encapsulation System: A Method to Remove Fragile Cells.- The Dialysis Encapsulation Process: The Role of Endocytosis.- Use of Fluorescent Probes for Describing the Process of Encapsulation by Hypotonic Dialysis.- Properties of Hypotonized, Crosslinked and Crosslinked-Permeabilized Rat Erythrocytes As Potential Carrier Systems.- Membrane Properties of Senescent and Carrier Human Erythrocytes.- Studies with Biotinylated RBC: (1) Use of Flow Cytometry to Determine Posttransfusion Survival and (2) Isolation Using Streptavidin Conjugated Magnetic Beads.- Resealed Erythrocytes as a Tool for Basic Studies.- Resealing of Protein Tyrosine Kinase Substrates Into Human Erythrocytes by Rapid Freezing and Thawing in Liquid Nitrogen.- The Metabolic Role of Glucose 1,6-P2 in Human Erythrocytes Studied by Encapsulation Procedures.- The Application of Newer Concepts of Oxygen Transport to the Evaluation of the Potential Utility of Reduced Hb-O2 Affinity.- Single Cell Analysis of Factors Increasing the Survival of Resealed Erythrocytes in the Circulation of Mice.- Entrapment of Purified ?-HemoglobinChains in Normal Erythrocytes as a Model for Human ?Thalassemia.- ATP Monitoring in Human Red Blood Cells with Luciferase Introduced Intracellularly.- Resealed Erythrocytes as Cellular Bioreactors.- Antagonism of the Lethal Effects of Cyanide with Resealed Erythrocytes Containing Rhodanese and Thiosulfate.- Acetaldehyde Oxidation by Aldehyde Dehydrogenase Loaded Erythrocytes.- Immunological Response to L-Asparaginase Loaded into Red Blood Cells.- Normalization of Hyperglycemia in Diabetic Mice by Enzyme-Loaded Erythrocytes.- Comparison of Uricase-Bound and Uricase-Loaded Erythrocytes as Bioreactors for Uric Acid Degradation.- Xenobiotic Detoxification by GSH-Loaded Erythrocytes.- A New Chemotherapeutic Agent: L-Asparaginase Entrapped in Red Blood Cells.- Resealed Erythrocytes as Advanced Drug Delivery Systems.- Rubomycin Loaded Erythrocytes in the Treatment of Mouse Tumor P388.- Erythrocytes as Carriers of New Anti-Opioid Prodrugs: In Vitro Studies.- Interactions of Carboplatin with Human Erythrocytes and Murine Erythroleukemic Cells.- Modulation of Thiopurine Metabolism in Native Human Erythrocytes.- Red Blood Cells as Advanced Drug Delivery Systems for Antiviral Nucleoside Analogues.- An Optimal Control Problem for the Administration of a Drug by Using Red Blood Cells as Bioreactors.- Site Specific Targeting of Resealed Erythrocytes.- Targeting of Erythrocytes to Cytotoxic T-Cells.- to In Vivo Targeting.- Erythrocytes as Carriers of Ricin A Chain: Effects on the Erythrophagocytic Cells.- In Vitro Targeting of Doxorubicin Loaded Canine Erythrocytes to Cytotoxic T-Lymphocytes (CTLL).- Pharmacokinetics of Doxorubicin Loaded and Glutaraldehyde Treated Erythrocytes in Healthy and Lymphoma Bearing Dogs.- Human and Veterinary Studies Using Resealed Erythrocytes.- Use ofGlutaraldehyde Treated Autologous Human Erythrocytes for Hepatic Targeting of Doxorubicin.- Clinical Evaluation of Glutaraldehyde-Treated Canine Erythrocytes in Normal Dogs.- Sickle Cells Modified by an Osmotic Pulse in the Presence of Inositol Hexaphosphate have Decreased Intracellular Hemoglobin Concentration and Decreased In Vitro Sickling without Prolonged In Vivo Survival.- A Baboon Model to Test Physiological and Adverse Effects of Human Red Cells Loaded with Inositol Hexaphosphate (IHP).- Susceptibility of Carrier Erythrocytes to a Natural hemolytic System.- Gd-DOTA Loaded into Red Blood Cells, a New Magnetic Resonance Imaging Contrast Agents for Vascular System.- Contributors.