HPMA
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HPMA
''N''-(2-Hydroxypropyl)methacrylamide or N-HPMA is the monomer used to make the polymer poly(''N''-(2-hydroxypropyl)methacrylamide). The polymer is water-soluble (highly hydrophilic), non-immunogenic and non-toxic, and resides in the blood circulation well. Thus, it is frequently used as macromolecular carrier for low molecular weight drugs (especially anti-cancer chemotherapeutic agents) to enhance therapeutic efficacy and limit side effects. Poly(HPMA)-drug conjugate preferably accumulates in tumor tissues via the passive-targeting process (or so-called EPR effect). Due to its favorable characteristics, HPMA polymers and copolymers are also commonly used to produce synthetic biocompatible medical materials such as hydrogels. The development of pHPMA as anti-cancer drug delivery vehicles is initiated by Dr. Jindřich Kopeček and colleagues at the Czech (-oslovak) Academy of Sciences in Prague in the mid-1970s. Prior to this, it was used as a plasma expander. The Kopeček Labo ...
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Jindřich Kopeček
Jindřich Henry Kopeček was born in Strakonice, Czech Republic, as the son of Jan and Herta Zita (Krombholz) Kopeček. He is distinguished professor of pharmaceutical chemistry and distinguished professor of biomedical engineering at the University of Utah in Salt Lake City, Utah. Kopeček is also an honorary professor at Sichuan University in Chengdu, China. His research focuses on biorecognition of macromolecules, bioconjugate chemistry, drug delivery systems, self-assembled biomaterials, and drug-free macromolecular therapeutics. Kopeček is regarded as one of the pioneers in development of biomedicinal polymers such as hydrogel implants and design of new polymer-drug conjugates. He was a key figure in a group which created the first clinically tested polymeric cancerostatics (PK1 and PK2). Hydrogels from his laboratory have been in clinical use. He was elected a member of the U.S. National Academy of Engineering in 2011 for contributions to the design of hydrogel biomateri ...
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Polymer-drug Conjugates
Polymer-drug conjugates are nano-medicine products under development for cancer diagnosis and treatment. There are more than 10 anticancer conjugates in clinical development. Polymer-drug conjugates are drug molecules held in polymer molecules, which act as the delivery system for the drug. Polymer drugs have passed multidrug resistance (MDR) testing and hence may become a viable treatment for endocrine-related cancers. A cocktail of pendant drugs could be delivered by water-soluble polymer platforms. The physical and chemical properties of the polymers used in polymer-drug conjugates are specially synthesized to flow through the kidneys and liver without being filtered out, allowing the drugs to be used more effectively. Traditional polymers used in polymer-drug conjugates can be degraded through enzymatic activity and acidity. Polymers are now being synthesized to be sensitive to specific enzymes that are apparent in diseased tissue. The drugs remain attached to the polymer and are ...
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Monomer
A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization. Classification Chemistry classifies monomers by type, and two broad classes based on the type of polymer they form. By type: * natural vs synthetic, e.g. glycine vs caprolactam, respectively * polar vs nonpolar, e.g. vinyl acetate vs ethylene, respectively * cyclic vs linear, e.g. ethylene oxide vs ethylene glycol, respectively By type of polymer they form: * those that participate in condensation polymerization * those that participate in addition polymerization Differing stoichiometry causes each class to create its respective form of polymer. : The polymerization of one kind of monomer gives a homopolymer. Many polymers are copolymers, meaning that they are derived from two different monomers. In the case of condensation polymerizations, t ...
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Polymer
A polymer () is a chemical substance, substance or material that consists of very large molecules, or macromolecules, that are constituted by many repeat unit, repeating subunits derived from one or more species of monomers. Due to their broad spectrum of properties, both synthetic and natural polymers play essential and ubiquitous roles in everyday life. Polymers range from familiar synthetic plastics such as polystyrene to natural biopolymers such as DNA and proteins that are fundamental to biological structure and function. Polymers, both natural and synthetic, are created via polymerization of many small molecules, known as monomers. Their consequently large molecular mass, relative to small molecule compound (chemistry), compounds, produces unique physical property, physical properties including toughness, high rubber elasticity, elasticity, viscoelasticity, and a tendency to form Amorphous solid, amorphous and crystallization of polymers, semicrystalline structures rath ...
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Hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are not attracted to water and may seem to be repelled by it. Hygroscopics ''are'' attracted to water, but are not dissolved by water. Molecules A hydrophilic molecule or portion of a molecule is one whose interactions with water and other polar substances are more thermodynamically favorable than their interactions with oil or other hydrophobic solvents. They are typically charge-polarized and capable of hydrogen bonding. This makes these molecules soluble not only in water but also in polar solvents. Hydrophilic molecules (and portions of molecules) can be contrasted with hydrophobic molecules (and portions of molecules). In some cases, both hydrophilic and hydrophobic properties occur in a single molecule. An example of these amphiphilic ...
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Immunogenic
Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injection of an antigen (the vaccine) provokes an immune response against the pathogen, protecting the organism from future exposure. Immunogenicity is a central aspect of vaccine development. * Unwanted immunogenicity is an immune response by an organism against a therapeutic antigen. This reaction leads to production of anti-drug-antibodies (ADAs), inactivating the therapeutic effects of the treatment and potentially inducing adverse effects. A challenge in biotherapy is predicting the immunogenic potential of novel protein therapeutics. For example, immunogenicity data from high-income countries are not always transferable to low-income and middle-income countries. Another challenge is considering how the immunogenicity of vaccines changes with ...
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Enhanced Permeability And Retention Effect
The enhanced permeability and retention (EPR) effect is a controversial concept by which molecules of certain sizes (typically liposomes, nanoparticles, and macromolecular drugs) tend to accumulate in tumor tissue much more than they do in normal tissues. The general explanation that is given for this phenomenon is that, in order for tumor cells to grow quickly, they must stimulate the production of blood vessels. VEGF and other growth factors are involved in cancer angiogenesis. Tumor cell aggregates as small as 150–200 μm, start to become dependent on blood supply carried out by neovasculature for their nutritional and oxygen supply. These newly formed tumor vessels are usually abnormal in form and architecture. They are poorly aligned defective endothelial cells with wide fenestrations, lacking a smooth muscle layer, or innervation with a wider lumen, and impaired functional receptors for angiotensin II. Furthermore, tumor tissues usually lack effective lymphatic drainage. ...
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Hydrogels
A hydrogel is a biphasic material, a mixture of porous and permeable solids and at least 10% of water or other interstitial fluid. The solid phase is a water insoluble three dimensional network of polymers, having absorbed a large amount of water or biological fluids. Hydrogels have several applications, especially in the biomedical area, such as in hydrogel dressing. Many hydrogels are synthetic, but some are derived from natural materials. The term "hydrogel" was coined in 1894. Chemistry Classification The crosslinks which bond the polymers of a hydrogel fall under two general categories: physical hydrogels and chemical hydrogels. Chemical hydrogels have covalent cross-linking bonds, whereas physical hydrogels have non-covalent bonds. Chemical hydrogels can result in strong reversible or irreversible gels due to the covalent bonding. Chemical hydrogels that contain reversible covalent cross-linking bonds, such as hydrogels of thiomers being cross-linked via disulf ...
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Plasma Expander
A volume expander is a type of intravenous therapy that has the function of providing volume for the circulatory system. It may be used for fluid replacement or during surgery to prevent nausea and vomiting after surgery. Physiology When blood is lost, the greatest immediate need is to stop further blood loss. The second greatest need is replacing the lost volume. This way remaining red blood cells can still oxygenate body tissue. Normal human blood has a significant excess oxygen transport capability, only used in cases of great physical exertion. Provided blood volume is maintained by volume expanders, a rested patient can safely tolerate very low hemoglobin levels, less than 1/3 that of a healthy person. The body detects the lower hemoglobin level, and compensatory mechanisms start up. The heart pumps more blood with each beat. Since the lost blood was replaced with a suitable fluid, the now diluted blood flows more easily, even in the small vessels. As a result of chemical ch ...
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Lysosomal
A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation center. Their primary responsibility is catabolic degradation of proteins, polysaccharides and lipids into their respective building-block molecules: amino acids, monosaccharides, and free fatty acids. The breakdown is done by various enzymes, for example proteases, glycosidases and lipases. With an acidic lumen limited by a single-bilayer lipid membrane, the lysosome holds an environment isolated from the rest of the cell. The lower pH creates optimal conditions for the over 60 different hydrolases inside. Lysosomes receive extracellular particles through endocytosis, and intracellular components through autophagy. They can also fuse with the plasma membrane and secrete their contents, a process called lysosomal exocytosis. After degradation ...
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Biopolymer
Biopolymers are natural polymers produced by the cells of living organisms. Like other polymers, biopolymers consist of monomeric units that are covalently bonded in chains to form larger molecules. There are three main classes of biopolymers, classified according to the monomers used and the structure of the biopolymer formed: polynucleotides, polypeptides, and polysaccharides. The Polynucleotides, RNA and DNA, are long polymers of nucleotides. Polypeptides include proteins and shorter polymers of amino acids; some major examples include collagen, actin, and fibrin. Polysaccharides are linear or branched chains of sugar carbohydrates; examples include starch, cellulose, and alginate. Other examples of biopolymers include natural rubbers (polymers of isoprene), suberin and lignin (complex polyphenolic polymers), cutin and cutan (complex polymers of long-chain fatty acids), melanin, and polyhydroxyalkanoates (PHAs). In addition to their many essential roles in living ...
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