Biomedical Applications of Immobilized Enzymes and Proteins, Softcover reprint of the original 1st ed. 1977
Volume 1

I) ADSORPTION EEEEEEEE E E carrier 2) COVALENT LINKAGE a) Insoluble support b) Intermolecular linkage N'E~ ~~ c) Soluble support 0 \:)....m 3) tM TRIX (MOLECULAR) ENTRAPMENT ~~~~~;;..,J~-polymer matrix 4) ENCAPSULATION membrane FIGURE I. Classification of immobilized enzymes. Covalently linked, adsorbed, and matrix-entrapped enzymes represent stage II, research on the microenvironment. Microencapsulation represents stage III, research on the intracellular environment. Further subdivision of microencapsulated enzymes will be found in Chapter 12. 4 T. M. S. CHANG matrix entrapment. In this section, detailed discussions will center on clinical analysis, urine analysis, monitoring of environmental pollution, radioimmune assay, enzyme-linked immunosorbent assay, enzyme electrodes, and other approaches involving immobilized enzymes, antibodies, and antigens. In the final section, research workers describe and discuss the perspectives of immobilized enzymes and proteins. Here, they speculate on the future potential of possible approaches, even though these may not have been extensively studied or tested at the laboratory stage. The biomedical applications of enzymes and proteins, especially in the thera­ peutic area, is in a very early stage of development. Much remains to be explored and studied, and the area is wide open for investigators interested in original research in a new interdisciplinary area. References Chang, T. M. S., 1972, Artificial Cells, Charles C. Thomas, Publisher, Springfield, Ill. Dunlop, R. B. (ed.), 1974, Immobilized Biochemicals and Affinity ChrOTIULtography, Plenum Press, N ew York.

1 Introduction.- I. Classification and Chemistries of Immobilized Enzymes.- 2 Covalent Linkage: I. Enzymes Immobilized by Covalent Linkage on Insolubilized Supports.- 1. Introduction.- 2. Methods of Enzyme Attachment.- 3. References.- 3 Covalent Linkage: II. Intramolecular Linkages.- 1. Introduction.- 2. Bifunctional Reagents.- 3. Condensation Reactions.- 4. References.- 4 Covalent Linkage: III. Immobilization of Enzymes by Intermolecular Cross-Linking.- 1. Introduction.- 2. Methodology.- 3. Advantages and Disadvantages.- 4. Properties.- 5. References.- 5 Immobilization of Enzymes by Adsorption.- 1. Introduction.- 2. Methodology.- 3. Advantages and Disadvantages.- 4. Properties of Adsorbed Enzymes.- 5. References.- 6 Gel-Entrapment of Enzymes.- 1. Introduction.- 2. Materials and Methods Used for Entrapping Enzymes.- 3. General Considerations Concerning Immobilization of Catalytic Material.- 4. References.- 7 Encapsulation of Enzymes, Cell Contents, Cells, Vaccines, Antigens, Antiserum, Cofactors, Hormones, and Proteins.- 1. Principles.- 2. Artificial Cells.- 3. Enzyme Kinetics and Stability.- 4. Variation in Membrane Materials and Configurations Used in the Encapsulation of Enzymes and Proteins.- 5. Variation of Contents in Encapsulated Enzyme-Protein Systems.- 6. References.- II. Experimental Applications in Therapy.- 8 Rationale and Strategies for the Therapeutic Applications of Immobilized Enzymes.- 1. Introduction.- 2. Biomedical Significance of Different Types of Immobilized Enzymes.- 3. Routes of Therapeutic Administration.- 4. Examples of Experimental Therapy.- 5. General.- 6. References.- 9 l-Asparaginase as a Model for Enzyme Therapy of Substrate-Dependent Tumors.- 1. Introduction.- 2. Historical Background.- 3. Distribution and Sources of l-Asparaginase.- 4. Some Properties of E. colil-Asparaginase EC-2 (l-Asparagine Amidohydrolase; EC 3.5.1.1).- 5. Spectrum of Sensitivity of Tumors to l-Asparaginase.- 6. Mechanism of Antitumor Action.- 7. Factors That Influence the Tumor-Inhibitory Effectiveness of l-Asparaginase.- 8. Use of l-Asparaginase in Acute Lymphocytic Leukemia Therapy.- 9. Problems Associated with l-Asparaginase Therapy.- 10. Combination Chemotherapy.- 11. Future Prospects and Perspectives.- 12. References.- 10 A Biomedical View of Enzyme Replacement Strategies in Genetic Disease.- 1. Introduction.- 2. Objective of the Campaign.- 3. Origins of Genetic Variation.- 4. Treatment Strategies.- 5. Principles and Pitfalls of Replacement Therapy.- 6. Comment.- 7. References.- 11 Experimental Therapy Using Semipermeable Microcapsules Containing Enzymes and Other Biologically Active Material.- 1. Introduction.- 2. Red Blood Cell Substitutes.- 3. Immobilized Urease as a Basic Model for Experimental Therapy in Vivo.- 4. Experimental Enzyme Replacement Therapy for Hereditary Enzyme Deficiency.- 5. l-Asparaginase for Substrate-Dependent Tumors.- 6. “One-Shot” Vaccine.- 7. Multienzyme Systems and Requirements for Cofactors.- 8. Immobilized Enzymes and Proteins for Artificial Kidney, Artificial Liver, and Detoxifier.- 9. References.- 12 Stabilized Urease Microencapsulated.- 1. Introduction.- 2. Urease Stabilization.- 3. Microencapsulation Technique.- 4. Experimental Procedure.- 5. Summary.- 6. References.- 13 Liquid-Membrane-Encapsulated Enzymes.- 1. Liquid Membrane System.- 2. Preparation of Encapsulated Enzymes.- 3. Catalytic Activity of Encapsulated Enzymes.- 4. Recovery of Enzymes and Denaturation Effects.- 5. Encapsulation of Multienzyme Systems and Whole Cells.- 6. Potential Applications.- 7. References.- 14 Liposomes as Carriers of Enzymes and Proteins in Medicine.- 1. Problems Associated with the Direct Administration of Proteins.- 2. Need for a Protein Carrier.- 3. Liposome as Carrier Candidate.- 4. Interaction of Protein-Containing Liposomes with the Biological Environment.- 5. Selective Targeting of Liposomes.- 6. Liposome-Entrapped Enzymes in the Treatment or Prevention of Disease.- 7. References.- 15 Enzyme-Loaded Erythrocytes.- 1. Introduction.- 2. Enzyme-Loaded Ghosts.- 3. Evaluation of Results.- 4. Summary.- 5. References.- 16 Enzyme Entrapment in Erythrocytes and Liposomes for the Treatment of Lysosomal Storage Diseases.- 1. Introduction.- 2. In Vivo Fate of Unentrapped Enzyme.- 3. Administration of Erythrocyte-Entrapped Enzyme.- 4. Administration of Liposome-Entrapped Enzyme.- 5. Biomedical Applications of Enzyme Entrapment: Enzyme Therapy.- 6. References.- 17 Strategy for Enzyme Therapy: Immobilization in Hypoallergenic Gel Versus Entrapment in Red Blood Cell.- 1. Gel Immobilization System.- 2. Red Blood Cell Entrapment System.- 3. Summary and Conclusions.- 4. References.- 18 Immobilized Enzymes for Therapeutic Applications and for Large-Scale Production of Biologically Active Compounds.- 1. Introduction.- 2. Therapeutic Applications.- 3. Production and Purification of Biologically Active Compounds.- 4. References.- 19 Artificial Kidney, Artificial Liver, and Detoxfiers Based on Artificial Cells, Immobilized Proteins, and Immobilized Enzymes.- 1. Introduction.- 2. Basic Principles.- 3. Use of Microencapsulated Enzymes for the Conversion of Waste Metabolites and Toxins.- 4. Immobilization of Albumin on Microencapsulated Adsorbents.- 5. Discussion.- 6. References.- 20 Removal of Bilirubin from Blood by Affinity-Competition Chromatography over Albumin-Agarose Gel.- 1. Introduction.- 2. Rationale.- 3. Preparation of Albumin-Agarose Gels.- 4. In Vitro Binding Studies.- 5. Removal of Bilirubin in Vivo.- 6. Specificity and Biocompatibility.- 7. Unresolved Problems.- 8. Future Applications.- 9. Summary.- 10. References.- 21 Membrane-Immobilized Liver Microsome Drug Detoxfier.- 1. Introduction.- 2. Preparation and Characterization of Microsomal Drug Detoxification Enzymes.- 3. Experimental Simulation of in Vivo Drug Detoxification.- 4. References.- 22 Some in Vivo and in Vitro Studies of Biologically Active Molecules on Organic Matrixes for Potential Therapeutic Applications.- 1. Introduction.- 2. Reactor Design.- 3. References.- 23 Therapeutic Perspectives of Enzyme Reactors.- 1. Introduction.- 2. Development of Enzyme Technology—Promise of Things To Come.- 3. Current Research and Future Vistas—Realization of the Potential.- 4. Collagen-Enzyme Complexes as Vehicles for Therapeutic Enzymes.- 5. Clinical Studies of Collagen-Immobilized l-Asparaginase Reactors: Reduction of Canine Serum Asparagine Levels.- 6. Conclusion.- 7. References.- 24 Possible Roles of Enzymes in Development of a Fuel Cell Power Source for the Cardiac Pacemaker.- 1. Introduction.- 2. Clinical Requirements.- 3. Energy Sources and Needs.- 4. Theory of Biofuel Cells.- 5. Pacemaker Biofuel Cell Studies.- 6. Outlook.- 7. References.- 25 The Use of Enzymes for Oxygenator Membranes.- 1. Introduction.- 2. Methods.- 3. Results and Discussion.- 4. Discussion.- 5. Conclusions.- 6. Summary.- 7. References.