Charles G. Gebelein

Biotechnology and bioactive polymers

Polysaccharide Applications: Factors Affecting the Bacterial Activity of Saccharides and Polysaccharides Modified through Reaction with Organostannanes (C.E. Carraher et al.). Coagulation Properties of Chemically Modified Heparins (A.W. Stemberger et al.). Polypeptides and Biodegradable Polymers: Living Polymerization of Proteins (S. Dirlikov). Modulation of Phosphocholine Bilayer Structures (A. Singh et al.). Medical Diagnositic Applications:NonAqueous Polymeric Systems for Diagnositic Applications (A.F. Azhar et al.). Protein Purification by Selective Adsorption on Immobilized Pyridinium Ligands (T.T. Ngo). Controlled Release and Medicinal Applications: Advances in Antimicrobial Polymers and Materials (T.L. Vigo). The Release of 5Fluorouracil from Dextran and Xylan Systems (C.G. Gebelein et al.). 23 additional articles. Index.

Cosmetic and pharmaceutical applications of polymers

Cosmetic Applications: The Suitability and Regulation of Raw Materials for the Cosmetics Industry (M.R. Thomas). Applications of Polymers in Hair Care (G. Martino, F. Nowak). Applications in Both Cosmetics and Pharmaceuticals: Cosmetic Uses of Chitin and Chitosan (S. Hirano et al.). Polysaccharides (G.L. Brode). Pharmaceutical Applications: Hylan and Hylan Derivatives in Drug Delivery (N.E. Larsen et al.). Polymeric Controlled Drug Delivery Systems (A.G. Thombre). Liposomes as a Topical Drug Delivery System Evaluated by In Vitro Diffusion Studies (K. Egbaria, N. Weiner). Other Medical Related Applications: Medical Applications of Hyaluronan and Its Derivatives (E.A. Balazs). Hydrophilic Lubricious Coatings for Medical Applications (Y.L. Fan). Twentysix additional articles. Index.

Polymeric materials in medication

Methodologies in Polymeric Medication.- Tissue/Material Interactions of Biomedical Polymers.- Polymer-Controlled Drug Delivery Systems: Science and Engineering.- Fibrous Delivery Systems for Antimicrobial Agents.- Evaluation of Membrane Suitability in Transdermal Drug Delivery.- Diffusion Controlled Release of Drugs from Coated Drug Polymer Complex.- Kinetics of Drug Release from Glassy Polymers: Effect of Initially Nonuniform Drug Distribution.- The Role of Polymer Matrix Structure and Interparticle Interaction in Diffusion-Limited Drug Release.- Polymeric Anticancer Agents - An Overview.- The Controlled Release of 5-Fluorouracil from Acrylate Copolymers of 1-(N-2-Ethylmethacrylcarbamoyl)-5-Fluorouracil Monomer.- Halogenated Nucleic Acids: Biochemical and Biological Properties of Fluorinated Polynucleotides.- Toxicity and Tissue Distribution of MVE-2 in the Dog After Intravenous and Intraperitonal Administration.- Transformation of Mouse Fibroblast (T3T) Cells Employing the Oncogenic Simian Virus 40 (SV40) for Evaluation of Anticancer Compounds.- Screening of Platinum II Polymines as Antitumor Drugs Employing Cell Differation of Normal and Transformed 3T3 Cells.- Polymeric Derivatives of cis-Dichlorodiammineplatinum II Analogs Based on Polyvinylamine-co-vinylsulfonate as Model Carriers In the Drug Delivery Systems.- Soluble Excipients Assisting Dissolution of Drugs: Importance of Amorphous State.- Polymeric Hydroxamic Acids for Iron Chelators Therapy.- Oxygen Species Chemistry of Osmium Carbohydrate Polymers.- Synthetic Polymeric Inducers of Interferon.- Polypeptides as Drugs.- A Systematic Approach to Induce New Catalytic Activities in Proteins.- Branched Polypeptides with a Poly(L-Lysine) Backbone: Synthesis, Conformation, and Immunomodulation.- Contributors.

Applied bioactive polymeric materials

Overview of Synthetic and Modified Natural Bioactive Polymers.- Pesticide-Polymer Research: A Review of 1976-87.- Chitosan and Derivatives as Activators of Plant Cells in Tissues and Seeds.- Biodegradation of Hydroxylated Polymers.- Combined Matrix Concept in Delivery of Bioactive Polypeptides.- Metal-Promoted Hydrolysis of Polymeric Chelating Agents: Chelators on Demand.- Formation of Polymeric Antimicrobial Surfaces From Organo-Functional Silanes.- Development of Polymers with Anti-Infectious Properties.- Synthesis and Characterization of Polymers Having Steroid Sex Hormones As Pendent Moieties.- Novel Approaches and Applications of Steroid Hormone Delivery Via Poly(dimethylsiloxane).- Kinetics of Synthesis and Degradation of the Polymer Derived From Tetrachloroplatinate and Methotrexate.- The Release of 5-Fluorouracil from Polycaprolactone Matrices.- Synthesis of Antitumor Polysaccharides.- Biological Activities of Tin-Containing Saccharides and Polysaccharides.- Nucleic Acid Analogs for High Performance Liquid Chromatography.- Immune Modulating Effects of Poly(ICLC) in Mice, Monkeys and Man.- Effect of Tetramisole and Its Platinum Polyamine on Mice Infected With Encephalomyocarditis-Variant-D Virus.- Influence of Short Chain Phospholipid Spacers on the Properties of Diacetylenic Phosphatidylcholine Bilayers.- Graft Copolymers of Amino Acids Onto Natural and Synthetic Polymers.- Radiation and Photochemical Methods for Synthesizing Novel Bioactive Polymers for Medical Applications.- Surface Treatment of PMMA with Polyvinylpyrrolidone and a Titanium Compound and Its Effect on Blood Compatibility.- Urokinase:AT-III:PGE1:Methyl Dopa Complex Immobilized Albumin-Blended Chitosan Membranes - Antithrombotic and Permeability Properties.- Control of Skin Wound Contraction Rate by Critically Insoluble Collagen Matrices.- Contributors.

Bioactive Polymeric Systems, An Overview

The breadth of the bioactive polymeric systems is illustrated in this chapter. The area includes controlled-release systems, such as erodible systems, diffusion-controlled systems, mechanical systems, and microcapsules. Bioactive polymeric systems would also include biologically active polymers, such as natural polymers, synthetic polypeptides, pseudoenzymes, pseudonucleic acids, and polymeric drugs. In addition, the area can include immobilized bioactive materials, such as immobilized enzymes, antibodies, and other bioactive agents. Some potential examples of these systems and approaches are given.

The Release of 5-Fluorouracil from Polycaprolactone Matrices

The release of 5-fluorouracil (5-FU) from monolithic dispersions in poly(caproiactone), [FUPC], was studied and compared with the release of 5-FU from the copolymers of 1-(N-2-ethylmethacryIcarbamoyl)-5-fluorouracil, [EMCF], with methyl methacrylate, [MMA]. Whereas the EMCF:MMA copolymers always exhibited zero-order release of the 5-FU (i.e., constant level of drug released with time), the [FUPC] systems did not. Up to about 25% 5-FU, the [FUPC] systems exhibited a profile in which the 5-FU release was dependent on the square root of time. On the other hand, the EMCF:MMA copolymers showed a constant release of the 5-FU regardless of whether the sample was in a powdered or a pellet form. The release rates were also slower for the copolymer systems than for the monolithic FUPC systems, and much higher concentrations of the drug could be incorporated into the copolymer systems. These differences in the release profiles are caused by differences in the basic nature of the two kinds of systems and the mechanisms of the release of the 5-FU from each. These differences and the mechanisms of the release are discussed in detail.

The Synthesis of Some Potentiallly Blood Compatible Heparin-like Polymeric Biomaterials

When artificial polymeric implants are used in the human body, one of the most important factors is the blood compatibility. The polymeric biomaterials reported here were prepared by the cycloaddition reaction of chlorosulfonyl isocyanate (CSI) to unsaturated polymers, such as polybutadiene or polyisoprene, to give a poly(N-chlorosulfonyl beta-lactam) structure which could then be hydrolyzed to give a polyanionic polymer that contains sulfamate and carboxylate groups. Previous researchers have shown that this type of material can be used as an artificial anti-coagulant with activities fairly similar to those of bovine plasma, but somewhat lower than heparin. These polymeric compounds have many of the same functional groups that are found in heparin, and might be expected to behave in a manner similar to heparinized polymers. Unfortunately, most of the previously reported research on these heparinoids has involved water soluble polyelectrolytes which would not be useful as a potential blood vessel prosthesis. Our research has concentrated upon the use of partially reacted, insoluble polymeric systems, and lightly crosslinked polymers which might retain much of the anticoagulant properties found in the polyelectrolytes, but might also be usable as replacement blood vessels.

OVERVIEW OF SYNTHETIC AND MODIFIED NATURAL BIOACTIVE POLYMERS

The area of applied bioactive polymeric systems includes such diverse entities as controlled release systems (erodable systems, diffusion controlled systems, mechanical systems and microcapsules), and biologically active polymers, such as natural polymers, synthetic polypeptides, pseudo-enzymes, pseudo-nucleic acids and polymeric drugs. The area can also include immobilized bioactive materials, such as immobilized enzymes, antibodies and other bioactive agents and the area of artificial cells. This Chapter reviews the general field of biologically active synthetic and modified natural macro-molecules with an emphasis on their common characteristics, problems and applications. The areas reviewed include both medical and non-medical applications for both controlled release systems and polymers that exhibit direct biological activity.

Methodologies in Polymeric Medication

The range of polymeric systems that can be used in medication is discussed. These approaches include controlled release devices (such as erodable systems, diffusion controlled systems, mechanical systems and microcapsules), biologically active polymers (such as natural polymers, synthetic polypeptides, pseudo-enzymes, pseudo-nucleic acids and polymeric drugs), and immobilized bioactive materials (such as immobilized enzymes, antibodies and other bioactive agents). Some illustrations of these methodologies are presented.

Polymeric Drugs Containing 5-Fluorouracil and/or 6-Methylthiopurine. Chemotherapeutic Polymers. XI

The concept of polymeric drugs and their use in medication is much more recent than some of the other biomedical applications of polymers. In its simplest form, a polymeric drug is a polymer that contains a drug or chemotherapeutic unit as part of the polymer backbone, as a pendant group from the polymer chain or as a terminal group on the polymer chain. Hundreds of such compounds have been synthesized in the past few decades. In their more advanced forms, polymeric drugs could be complex copolymers of polymers attached to some natural substrate such as an imminoglobulin, a histone or a nucleic acid. Numerous reviews and books have appeared on this subject in the past decade (1–12). It would be beyond the scope of this present paper to attempt to review this rapidly developing field. We will concentrate primarily on polymers containing 5fluorouracil or 6-methylthiopurine and some closely related polymers. Prior to this, however, we will examine the basic concepts involved in polymeric drug medication.