Bioactive Polymeric Systems : An Overview

The vast array of libraries in the world bear mute witness to the truth of the 3000-year-old observation of King Solomon who stated " ... of making many books there is no end, and much study is a weariness of the flesh." Yet books are an essential written record of our lives and the progress of science and humanity. Here is another book to add to this huge collection, but, hopefully, not just another collection of pages, but rather a book with a specific purpose to aid in alleviating the "weariness of the flesh" that could arise from much studying of other journals and books in order to obtain the basic information contained herein. This book is about polymeric materials and biological activity, as the title notes. Polymeric materials, in the broad view taken here, would include not only synthetic polymers (e.g., polyethylene, polyvinyl chloride, polyesters, polyamides, etc.), but also the natural macromolecules (e.g., proteins, nucleic acids, polysaccharides) which compose natural tissues in humans, animals and plants. In the broad sense used here, biological activity is any type of such action whether it be in medication, pest control, plant-growth regu­ lation, and so on. In short, this book attempts to consider, briefly, the use of any type of polymeric material system with essentially any kind of biological activity.

Bioactive Polymeric Systems: An Overview.- Abstract.- 1. Introduction.- 2. Bioactive Polymeric Systems.- 2.1. What Is Bioactivity?.- 2.2. What Are Bioactive Polymeric Systems?.- 3. Classes of Bioactive Polymeric Systems.- 4. Polymeric Controlled-Release Systems.- 4.1. Erodible Systems.- 4.2. Diffusion-Controlled Systems.- 4.3. Mechanical Devices.- 4.4. Microcapsules.- 5. Biologically Active Polymers.- 5.1. Natural Polymers.- 5.2. Synthetic Polypeptides.- 5.3. Pseudoenzymes.- 5.4. Pseudonucleic Acids.- 5.5. Polymeric Drugs.- 6. Immobilized Bioactive Materials.- 6.1. Immobilized Enzymes.- 6.2. Other Immobilized Bioagents.- 7. Examples of Bioactive Polymeric Systems.- 7.1. Many Uses for Any System.- 7.2. Many Solutions for Any Problem.- 8. Summary.- 9. References.- 2. Biocompatibility of Bioactive Polymeric Systems.- 1. Types of Bioactive Polymeric Systems.- 2. Biocompatibility ―General Considerations.- 3. Primary Acute Toxicity Screening.- 4. Tissue-Interaction Studies.- 5. Summary.- 6. References.- 3. Controlled-Release Pesticides: A Historical Summary and State of the Art.- Abstract.- 1. Antifouling.- 1.1. Toxic Paints.- 1.2. Organotin Antifoulants.- 1.3. Antifouling Rubber.- 1.4. Extension of the Concept.- 1.5. Further Developments in Antifouling Paint Technology.- 1.6. Mixed-Agent Paints.- 1.7. Notes on Antifouling Paint Technology.- 1.8. Organometallic Polymers.- 2. Molluscicidal Elastomers.- 2.1. Snail-Borne Parasitic Disease.- 2.2. Controlled-Release Organotin Molluscicides.- 2.3. Technology Based upon Organotin/Elastomer Development.- 2.4. Organotin Properties: Toxicology and Chemodynamics.- 2.5. Controlled-Release Cercariacides.- 2.6. Other Controlled-Release Molluscicides.- 2.7. Controlled-Release Copper Sulfate Elastomers.- 2.8. Critique.- 2.9. Bait Molluscicides.- 3. Controlled-Release Insecticidal Elastomers.- 4. Bactericidal and Fungicidal Elastomers.- 5. Herbicidal Elastomeric Formulations.- 6. Controlled-Release Thermoplastic Systems: An Overview.- 7. Early Concepts.- 8. Carrier Systems: Insecticides.- 8.1. Insecticidal Strip.- 8.2. Flea Collars.- 8.3. Insecticidal Roach Tape and Related Inventions.- 9. Insecticidal and Molluscicidal Monoliths.- 9.1. The Porosigen Concept and Controlled Release.- 10. Thermoplastic Aquatic Herbicide Systems.- 11. Controlled Release through Pendent Substitution.- 12. Controlled-Release Juvenile Hormones.- 13. Monoliths in Agriculture.- 14. Agricultural Uses of Porosigen-Containing Monoliths.- 15. Microencapsulation.- 16. Pendent Systems in Agriculture.- 17. Pheromones in Agriculture.- 18. Insecticidal Carrier Systems.- 19. Other Release Systems.- References.- 4. Controlled Release of Antifertility Agents.- Abstract.- 1. Introduction.- 2. Injectables.- 2.1. Suspensions.- 2.2. Biodegradable Microspheres.- 2.3. Polymer-Steroid Complexes.- 3. Subdermal Implants.- 3.1. Nonbiodegradable Implants.- 3.2. Biodegradable Implants.- 4. IUDs.- 4.1. Nonmedicated IUDs.- 4.2. Copper-Bearing IUDs.- 4.3. Steroid-Releasing IUDs.- 5. Intravaginal Devices.- 6. Intracervical Devices.- 7. Oral Contraceptives.- 8. Topical Application.- 9. Intranasal Applications.- 10. Transcervical Device.- 11. Immunological Response.- References.- 5. Controlled Release and Plant-Growth Regulators.- Abstract.- 1. Introduction.- 2. Plant-Growth Regulators.- 2.1. Auxins.- 2.2. Gibberellins.- 2.3. Cytokinins.- 2.4. Inhibitors.- 2.5. Ethylene Gas.- 3. The ControUed-Release Concept.- 3.1. Physical Methods.- 3.2. Chemical Methods.- 4. The Present State of the Art of Controlled-Release Plant-Growth Regulators.- 5. The Future.- 5.1. Long-life Crops.- 5.2. Seasonal Crops.- 5.3. Environmental Vigor.- 5.4. Improving Herbicide and Fertilizer Efficiency.- 5.5. Promotion of Early Germination.- 5.6. Protection from Degradation.- 6. Conclusions.- References.- 6. Hydrogels for Controlled Drug Release.- Abstract.- 1. Introduction.- 2. Reservoir Devices.- 3. Monolithic Devices (Dissolved Systems).- 4. Monolithic Devices (Drug-Dispersed Systems).- 5. Monolithic Devices with Barrier Layer.- 6. Novel Drug Delivery Systems.- References.- 7. Biodegradable Drug Delivery Systems Based on Polypeptides.- Abstract.- 1. Introduction.- 1.1. Historical Background.- 1.2. Advantages and Disadvantages.- 1.3. Chemical Types.- 2. Poly (?-Amino Acids).- 3. Synthesis of Poly (?-Amino Acids) and Drug Conjugates.- 3.1. Polymer Backbone.- 3.2. Attachment of Norethindrone onto Poly (L-Glutamic Acid).- 3.3. Attachment of Spacer Groups onto Poly (L-Glutamic Acid).- 3.4. Attachment of Bioactive Steroids onto Spacer Groups.- 3.5. Other Polymer/Drug Conjugates Based on Poly(Hydroxyalkylglutamines).- 3.6. Copolymerization of L-Glutamic Acid and l-Valine.- 3.7. Copolymer/Drug Conjugates.- 4. Dosage-Form Formulation and Drug Release.- 4.1. Dosage Forms.- 4.2. In vitro Drug Release.- 4.3. In vivo Drug Release.- 5. Toxicity Studies.- 6. Other Biodegradable Polymer/Drug Conjugates.- 7. Drug Targeting.- 8. Conclusions.- References.- 8. Controlled-Release Animal Repellents in Forestry.- Abstract.- 1. Introduction.- 1.1. Animal Damage in Forestry.- 1.2. Repellent Systems.- 2. Selenium as a Timed-Release Systemic Repellent.- 2.1. Biochemistry of Selenium.- 2.2. Formation of Timed-Release Browse Deterrents.- 3. Characterizing the Performance of Controlled-Release Animal Repellents.- 3.1. Nature of the Problem.- 3.2. Mathematical Analysis.- 4. Future Impact of Bioactive Polymers in Forestry.- 4.1. Animal Repellents.- 4.2. Other Applications.- References.- 9. Affinity Chromatography.- 1. Introduction.- 2. The Constituents of the Ideal Affinity Adsorbent.- 2.1. The Matrix.- 2.2. The Spacer Molecule.- 2.3. The Ligand.- 3. The Synthesis of Affinity Adsorbents.- 4. The Chromatographic Properties of Affinity Adsorbents.- 4.1. Adsorption of Complementary Biomolecules.- 4.2. Bioselective Elution.- 5. Applications of Affinity Chromatography.- 5.1. Protein Purification.- 5.2. Purification of Supramolecular Structures.- 5.3. Isoenzyme Resolution.- 5.4. Removal of Contaminants.- 5.5. Resolution of Mutant Proteins.- 5.6. Concentration of Dilute Solutions.- 5.7. Resolution of Chemically Modified Staphylococcal Nuclease from Native Proteins.- 5.8. Estimation of Dissociation Constants.- 5.9. Studies on Enzyme Kinetic Mechanisms.- 5.10. Clinical Applications.- 6. High-Performance Liquid Affinity Chromatography (HPLAC).- 7. Conclusions.- References.- 10. Application of Radiation Grafting in Reagent Insolubilization.- Abstract.- 1. Introduction.- 2. Principle of Radiation Grafting Insolubilization Method.- 3. Radiation Grafting Procedures.- 3.1. Pre-Irradiation Techniques for Grafting.- 3.2. Mutual or Simultaneous Radiation Grafting Method.- 4. Typical Experimental Grafting Methods.- 4.1. Pre-Irradiation Grafting.- 4.2. Mutual or Simultaneous Grafting.- 5. Choice of Grafting Method for Insolubilization Reactions.- 6. Variables Influencing Simultaneous Grafting.- 6.1. Role of Solvent.- 6.2. Significance of Dose Rate and Dose.- 7. Additive Effects in Grafting.- 7.1. Acid Effects in Grafting.- 7.2. Polyfunctional Monomers as Additives in Grafting.- 7.3. Combined Effects of Acid and Polyfunctional Monomers.- 7.4. Miscellaneous Additives to Reduce Homopolymerization.- 8. Application of Radiation Grafting to Enzyme Insolubilization.- 9. Application of Grafting to Heterogenization of Complexes.- 10. Application of Grafting to Insolubilization of Analytical Reagents.- 11. General Conclusions.- References.- 11. Immobilized Enzymes.- Abstract.- 1. Introduction.- 2. Supports.- 3. Methods of Immobilization.- 3.1. Adsorption.- 3.2. Cross-linking.- 3.3. Adsorption-Cross-linking.- 3.4. Covalent Bonding.- 3.5. Entrapment.- 3.6. Microencapsulation.- 3.7. Electrochemical Methods.- 4. Properties of Immobilized Enzymes.- 4.1. Physical Properties.- 4.2. Chemical Properties.- 4.3. Stability.- 4.4. Specificity.- 5. Uses of Immobilized Enzymes.- 5.1. Industrial Applications.- 5.2. Analytical Applications.- 5.3. Structure-Function Studies.- 5.4. Therapeutic Applications.- 6. Future Directions.- References.- 12. Biomedical Polypeptides―A Wellspring of Pharmaceuticals.- Abstract.- 1. Introduction.- 2. Methods of Peptide Synthesis.- 2.1. Chemical Synthesis.- 2.2. Biological Synthesis.- 2.3. Semisynthesis.- 3. Structural and Conformational Specificity.- 3.1. Peptide Structure: Polyamide Backbone with Various Side Chains.- 3.2. The Contribution of Sequence to Biological Specificity.- 3.3. Contribution of Peptide Conformation to Biologic Specificity.- 4. Modifications of Peptides to Enhance Therapeutic Utility.- 4.1. Motives for Peptide Modification.- 4.2. Enhancement of Resistance to Proteolytic Degradation.- 4.3. Enhancement of Selectivity by Chain Shortening to Remove Undesirable Message Sequences.- 4.4. Enhancement of Potency and Selectivity by Side-Chain Modification.- 4.5. Enhancement of Potency and Selectivity by Peptide-Backbone Modification to Promote Bioactive Conformation.- 4.6. Enhancement of Potency and Selectivity with Peptide Oligomers.- 4.7. Enhancement of Potency with Peptide Analogues Displaying Superior Membrane Permeability.- 5. Physicochemical Vehicles to Modulate Proteolysis and Absorption.- 6. Modes of Pharmacologic Control of Endogenous Peptidergic Processes.- 6.1. Inhibition of Ribosomal Translation.- 6.2. Modulation of Posttranslational Processing.- 6.3. Modulation of Peptide Release: Peptide Release Factors, Release Inhibitors, and Their Antagonists.- 6.4. Enhancement of Endogenous Peptide Levels by Blocking Degradation.- 6.5. Feedback Inhibitors.- 6.6. Common Dosage Problems with Endogenous Peptide Modulation.- 7. Peptide Analogues with Increased Duration of Action.- 8. Types of Therapeutic Biomedical Polypeptides.- 8.1. Peptide Hormones and Neurotransmitters.- 8.2. Peptidase and Proteinase Inhibitors.- 8.3. Antigenic Peptides as Synthetic Vaccines.- 8.4. Peptide Ionophoric Antibiotics.- 8.5. Peptide Chemoattractant Immunostimulants.- 8.6. Flavorful and Poisonous Peptides.- 9. Conclusion.- References.- 13. Drug Delivery with Protein and Peptide Carriers.- Abstract.- 1. Introduction.- 2. Preparation of Drug-Carrier Complexes.- 3. Chemical and Biological Properties.- 4. Mechanisms of Action and Pharmacological Properties.- 5. Conclusion.- References.- 14. Biomedical Applications of Polysaccharides.- Abstract.- 1. Structure and Physical Properties.- 2. Applications in Biochemistry.- 3. Uses as Surface-Acting Drugs and in Medicinal Formulations.- 4. Uses in Blood, Body Fluids, and Biomaterials, and in Trauma.- 5. Physiological Functions, Immunological Relationships, and Vaccines.- 6. Textiles, Membranes, Microencapsulation, Controlled-Release Agents, and Targeted Drugs.- References.- 15. Interferon Induction by Polymers.- 1. Introduction.- 2. Types of Polymers.- 2.1. Polycarboxylic Acids.- 2.2. Polysaccharides.- 2.3. Nucleic Acids.- 3. Effect of Size of Components on Effectiveness of Poly(ICLC).- 3.1. Molecular Characteristics of Poly(ICLC) as a Function of the Component Size.- 4. Effect of Inducers on the Immune System-Antibody Production.- 5. Effects on Cell-Mediated Immunity.- 6. Interferon Inducers and Human Disease.- 6.1. Polyinosinic-Polycytidylic Acid [Poly(I)-Poly(C)].- 6.2. Polyinosinic-Polycytidylic Acid-Poly-L-Lysine [Poly(ICLC)].- References.- 16. Functionality and Applicability of Synthetic Nucleic Acid Analogues.- Abstract.- 1. Introduction.- 2. Synthesis and Properties of Polyamino Acids Containing Nucleic Acid Bases.- 2.1. Polymer Synthesis.- 2.2. Conformations of the Polymers.- 2.3. Polymer-Polymer Interaction between Nucleic Acid Base-Substituted Poly-L-Lysines.- 2.4. Polymer-Polymer Interactions between Nucleic Acid Base-Substituted Poly-L-Lysine and Other Synthetic Polymers.- 2.5. Isopoly-L-Lysine Having Pendant Nucleic Acid Bases.- 3. Photochemistry of the Polymers Containing Thymine Bases.- 3.1. Fundamental Study on Photodimerization.- 3.2. Effect of Complementary Bases.- 3.3. Photoreaction of the Polymers Having Cyanouracil Units.- 4. Synthesis and Properties of Polyethyleneimine Derivatives Containing Nucleic Acid Bases.- 4.1. Polymer Synthesis.- 4.2. Interaction of the Graft Polymers.- 4.3. Further Studies on Polyethyleneimine Having Thymine Bases.- 5. Functionality and Applicability of the Supported Nucleic Acid Bases as Polymeric Reagents.- 6. Cyclic Derivatives of Pyrimidine Bases.- 7. Conclusion.- References.- 17. Enzyme-Mimetic Polymers.- Abstract.- 1. Introduction.- 2. Polymer Catalysts That Bind the Substrate.- 2.1. Polymer Catalyst Having a Substrate-Binding and a Catalytic Group.- 2.2. Reactions Occurring under Circumstances Regulated by Polymers.- 2.3. Stereospecific Micellar Reactions.- 2.4. Chemical Reactions in Organized Molecular Assemblies.- 2.5. Polymeric Coenzymes.- 2.6. Metalloenzyme Models.- 3. Intramolecular Cooperation between Binding Site and Catalytic Site along a Polymer Chain.- 3.1. Linear Polymer Catalysts.- 3.2. Cyclic Polymer Catalysts.- 3.3. Intramolecular Catalysis.- 4. Multifunctional and Multiple Polymer Catalysts.- 4.1. Bifunctional Catalyses.- 4.2. Polymeric Multiple Catalysts.- 4.3. Cyclic Multiple Catalysts.- 5. Intrachain Reactions Proceeding on a Polymer Chain.- 5.1. Intrachain Reactions among Functional Groups Distributed along a Polymer Chain.- 5.2. Intrachain Reaction of Pairs of Functional Groups Attached to the Chain Ends ― Statistical Treatments.- 5.3. Intrachain Reactions of Pairs of Functional Groups Attached to the Chain Ends ―Dynamic Treatments.- Symbols.- References.- 18. Bioactive Carboxylic Acid Polyanions.- Abstract.- 1. Introduction.- 2. Types of Carboxylic Acid Polymers Evaluated for Biological Activity.- 2.1. Homopolymers.- 2.2. Copolymers of Maleic Anhydride.- 2.3. Other Carboxylic Acid Copolymers.- 2.4. Carboxylic Acid-Half-Amide and Imide Polymers.- 3. Effect of Molecular Weight and Structure of Polycarboxylic Acid Polymers on Biological Activity.- 4. Macrophage Activation by Polycarboxylic Acid Polymers.- 5. Distribution of Polyanions in the Host.- 6. Cellular Uptake of Polycarboxylic Acid Polymers.- 7. Clinical Effects of Polycarboxylic Acid Polymers.- 8. Summary.- References.- 19. Polymeric Antitumor Agents on a Molecular and Cellular Level.- 1. Introduction.- 1.1. Definition: Molecular Level ― Cellular Level.- 1.2. Tumor Cells and Tumor Therapy.- 1.3. The Carrier Concept.- 2. Antitumor Agents on a Molecular Level.- 2.1. Model for a Polymeric Drug Carrier.- 2.2. How Do Macromolecules Enter Cells?.- 2.3. Polymeric Carriers.- 2.4. Affinity Chemotherapy.- 2.5. From Research Lab to Clinic?.- 3. Polymeric Antitumor Agents on a Cellular Level.- 3.1. Death of a Tumor Cell-How To Duplicate this Event.- 3.2. Stable Synthetic Bilayer Membranes via Polymerization.- 3.3. How To Improve Biological Functionality.- 4. Conclusion.- References.- 20. Biological Activities of cis-Dichlorodiamineplatinum II and Its Derivatives.- Abstract.- 1. Introduction.- 2. General Discussion.- 3. Structural Requirements.- 4. Mode of Activity.- 5. Animal and Human Toxicity.- 6. Antineoplastic Effects.- 7. Toxicity Minimization.- 8. Rationale.- 9. Synthesis.- 10. Physical and Structural Characterization.- 11. Biological Characterization.- Abbreviations.- References.- 21. Iron-Complexing Bioactive Polymers.- Abstract.- 1. Introduction.- 2. Medical Problems of Iron Overload.- 3. Naturally Occurring Iron Chelators.- 4. Programs for the Development of New Iron Chelators.- 5. Development of Polymeric Iron Chelators for Iron Chelation Therapy.- 5.1. Hydroxamic Acid Type.- 5.2. Phenol Type.- 5.3. Catechol Type.- 6. Selection of Iron Chelating Polymers for Potential Use in Iron Chelation Therapy.- 7. Iron Chelating Ability of Polymeric Iron Chelators.- 8. Bioassays of Iron Chelating Drugs.- 9. Results of Bioassays for Polymeric Iron Chelators.- 10. Organizations Supporting the Development of New Iron Chelators.- References.- 22. Biological Activities and Medical Applications of Metal-Containing Macromolecules.- Abstract.- 1. ...