Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluosol (Alpha Therapeutic Corporation, Los Angeles, CA) an emulsion of perfluorocarbons with a high oxygen-carrying capacity, was approved as an adjunct to alleviate myocardial ischemia during coronary angioplasty. This drug also significantly enhances myocardial salvage presumably related to an action on the neutrophil. The mechanism by which fluosol and its individual components, including the detergent Pluronic F-68, affected neutrophil function was examined. During the incubation of neutrophils with fluosol, a rapid stimulation of superoxide anion production and degranulation which progressively increased over a 30-minute period was detected. Neutrophils incubated with only Pluronic F-68 produced similar amounts of superoxide anion. Cytochalasin B, an inhibitor of phagocytosis, significantly inhibited this superoxide anion generation. As shown previously, neutrophils incubated with fluosol for 30 minutes and then subsequently stimulated manifested a reduction in lysozyme release as compared with untreated cells. Results of an electron microscopic examination confirmed the cellular uptake of the fluosol within phagocytic vacuoles. Neutrophil viability determined by trypan blue was unaffected after fluosol treatment. These observations show that the fluosol emulsion, primarily through micelles formed by the detergent Pluronic F-68, activates human neutrophils by serving as a phagocytic stimulus, which produces a cell refractory to subsequent stimulation.
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PMID:Phagocytic activation of human neutrophils by the detergent component of fluosol. 131 83

Perfluorochemicals are substances with small particle size, low viscosity, and high oxygen-carrying capacity. The role of one perfluorochemical preparation. Fluosol, an emulsion of two perfluorocarbons, a detergent Pluronic F-68 (poloxamer 188), and phospholipids on myocardial reperfusion injury was investigated in a closed-chest canine model of regional ischemia. Intracoronary and intravenous infusions of Fluosol in the perireperfusion period significantly reduced infarct size and improved ventricular function in animals that were examined for up to 2 weeks after reperfusion. Fluosol preserved endothelial structure and endothelium-dependent relaxation of large and small vessels. Fluosol reduced neutrophil plugging of capillaries and attenuated neutrophil infiltration into the reperfused bed. Ex vivo studies of neutrophil function demonstrated apparent suppression of chemotaxis and lysozyme degranulation in cells from animals that were treated with Fluosol. However, treatment of cells in vitro manifested enhanced superoxide anion production within 5 minutes of incubation even with low concentrations of Fluosol. This effect was found to be almost entirely attributable to the detergent, Pluronic F-68. The stimulation of neutrophils by Fluosol was found to result directly from phagocytosis and indirectly from activation of the complement cascade. These findings suggest that perfluorochemicals may provide a novel form of therapy to enhance myocardial salvage after successful reperfusion. The mechanism appears to be due to stimulation and subsequent "deactivation" of neutrophils peripherally, which thereby reduces their cytotoxic potential in the reperfused myocardium. The role of the oxygen-carrying ability of the perfluorocarbons in the reduction of reperfusion injury remains to be determined. In a pilot study in human beings, Fluosol that was used as adjunctive therapy with angioplasty has also been shown to improve regional ventricular function. Clinical trials with perfluorochemical emulsions appear warranted to determine the role of reperfusion injury in limiting myocardial salvage in patients who are undergoing pharmacologic or mechanical reperfusion.
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PMID:Role of perfluorochemical emulsions in the treatment of myocardial reperfusion injury. 144 6

A series of proteins and one membrane-bound peptide have been partitioned in aqueous two-phase systems consisting of micelle-forming block copolymers from the family of Pluronic block copolymers as one polymer component and dextran T500 as the other component. The Pluronic molecule is a triblock copolymer of the type PEO-PPO-PEO, where PEO and PPO are poly(ethylene oxide) and poly(propylene oxide), respectively. Two different Pluronic copolymers were used, P105 and F68, and the phase diagrams were determined at 30 degrees C for these polymer systems. Since the temperature is an important parameter in Pluronic systems (the block copolymers form micellar-like aggregates at higher temperatures) the partitioning experiments were performed at 5 and 30 degrees C, to explore the effect of temperature-triggered micellization on the partitioning behaviour. The temperatures correspond to the unimeric (single Pluronic chain) and the micellar states of the P105 polymer at the concentrations used. The degree of micellization in the F68 system was lower than that in the P105 system, as revealed by the phase behaviour. A membrane-bound peptide, gramicidin D, and five different proteins were partitioned in the above systems. The proteins were lysozyme, bovine serum albumin, cytochrome c, bacteriorhodopsin and the engineered B domain of staphylococcal protein A, named Z. The Z domain was modified with tryptophan-rich peptide chains in the C-terminal end. It was found that effects of salt dominated over the temperature effect for the water-soluble proteins lysozyme, bovine serum albumin and cytochrome c. A strong temperature effect was observed in the partitioning of the integral membrane protein bacteriorhodopsin, where partitioning towards the more hydrophobic Pluronic phase was higher at 30 degrees C than at 5 degrees C. The membrane-bound peptide gramicidin D partitioned exclusively to the Pluronic phase at both temperatures. The following trends were observed in the partitioning of the Z protein. (i) At the higher temperature, insertion of tryptophan-rich peptides increased the partitioning to the Pluronic phase. (ii) At the lower temperature, lower values of K were observed for ZT2 than for ZT1.
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PMID:Aqueous two-phase systems containing self-associating block copolymers. Partitioning of hydrophilic and hydrophobic biomolecules. 1032 23

Paclitaxel (Taxol)-containing chitin and chitin-Pluronic F-108 microparticles were formulated as biodegradable systems for localized administration in solid tumors. The microparticles were characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and swelling studies in phosphate-buffered saline (PBS, pH 7.4). Lysozyme-induced degradation and in vitro release of paclitaxel was examined in PBS at 37 degrees C. The percent change in tumor volume was used to assess efficacy of the Formulations after local administration in murine Lewis lung carcinoma model. FT-IR confirmed higher degree of acetylation in chitin microparticles from the starting chitosan sample and the SEM showed that the chitin-Pluronic F-108 microparticles were significantly more porous than chitin microparticles. Due to higher porosity, chitin-Pluronic microparticles were able to imbibe higher swelling medium and degraded much faster in the presence of lysozyme than chitin microparticles. After 48 h. 51% of incorporated paclitaxel was released from chitin-Pluronic microparticles as compared to 28% from chitin microparticles. In vivo studies in Lewis lung carcinoma-bearing mice showed that the tumor volumes after 6 days using paclitaxel-loaded chitin and chitin-Pluronic F-108 microparticles was 458 and 307 mm3, respectively. In contrast, the tumor volume was 997 mm3 for the untreated control. The results of this study show that chitin and chitin-Pluronic F-108 microparticles are biodegradable drug delivery systems that can be useful for localized delivery of paclitaxel in solid tumors.
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PMID:Localized delivery of paclitaxel in solid tumors from biodegradable chitin microparticle formulations. 1205 22

A model is developed to describe protein release kinetics from injectable, polymer solution depots which undergo rapid phase inversion on injection. The model consists of a polymer-rich phase and a solvent-rich phase, consistent with experimentally observed phase inversion morphology. Equations in the polymer-rich phase are based on diffusion-reaction mass balances for solvent, water and dissolved drug, and the rate of dissolution of dispersed drug particles. Equations in the water-rich phase are also of the diffusion-reaction type. Transport parameters in the polymer-rich phase are coupled to the ternary thermodynamics through friction formalism, and remaining parameters are estimated from literature data, leaving two free parameters: volume fraction of water-rich phase (epsilon) and k, the mass-transfer coefficient for bath-side transfer of the protein. Variations of these parameters lead to predictions of release profiles that vary from a rapid, burst-like behavior followed by a locking-in of the polymer-rich phase, to a uniform, zero-order profile. Comparisons are made to lysozyme release data for three systems: PLGA solutions in N-methlypyrollidinone (NMP), PLA solutions in NMP, and the latter with added Pluronic. Good agreement between model predictions and data is shown; in particular, the transition from rapid release to zero-order kinetics that occurs on addition of Pluronic is illustrated.
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PMID:A model for drug release from fast phase inverting injectable solutions. 1565 41

Thermo-sensitive and biodegradable hydrogels based on Pluronic tri-block copolymers were prepared by a photo-polymerization method. Two terminal hydroxyl groups in Pluronic F-127 were acrylated to form a Pluronic macromer. Photo-cross-linked Pluronic hydrogels prepared by UV radiation showed a gradually decreased swelling ratio with increasing temperature and exhibited a thermally-responsive change in the swelling ratio when the temperature was cycled between 10 degrees C and 37 degrees C. These hydrogels degraded slowly due to the cleavage of ester linkage in the acrylated Pluronic terminal end. When lysozyme, a model protein drug, was loaded in the hydrogels, bi-phasic protein release profiles were attained: a burst-free and rapid controlled release profile was initially observed for a one week period and a much slower sustained release was followed thereafter. The release rates could be controlled by varying the amount of Pluronic macromer for photo-polymerization.
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PMID:Photo-crosslinkable, thermo-sensitive and biodegradable pluronic hydrogels for sustained release of protein. 1569 1

A new, facile method to prepare the heparin-functionalized PLGA nanoparticle (HEP-PLGA NP) for the controlled release of growth factors is developed. This system is composed of PLGA as a hydrophobic core, Pluronic F-127 as a hydrophilic surface layer, and heparin as the functional moiety. HEP-PLGA NPs were prepared by a solvent-diffusion method without chemical modification of the components. The entrapment of heparin molecules was confirmed by a negatively increased zeta potential value and the specific binding affinity to antithrombin III. The average diameter and the surface charge of the nanoparticles were ranged from 139+/-2 to 188+/-4 nm and from -26.0+/-1.1 to -44.1+/-1.3 mV by increasing the amount of heparin during the nanoparticle preparation. Accordingly, the amount of heparin on the nanoparticle increased from 0% to 4.7%. As a model in vitro release experiment, lysozyme was loaded into HEP-PLGA NPs, and a sustained release profile over 2 weeks was obtained with maintaining its bioactivity. The release of rhVEGF, one of the heparin-binding growth factors, showed a more sustained and prolonged profile than that of lysozyme over one month.
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PMID:A facile method to prepare heparin-functionalized nanoparticles for controlled release of growth factors. 1636 Feb 4

On the basis of elastic light scattering, we have compared the capacity of the multi-block, surfactant copolymers Poloxamer 108 (P108), Poloxamer 188 (P188), and Tetronic 1107 (T1107), of average molecular weight 4700, 8400, and 15,000, respectively, with that of polyethylene glycol (PEG, molecular weight 8000) to suppress aggregation of heat-denatured hen egg white lysozyme (HEWL) and bovine serum albumin (BSA). We also compared the capacity of P188 to that of PEG to suppress aggregation of carboxypeptidase A denatured in the presence of trifluoroethanol and to facilitate recovery of catalytic activity. In contrast to the multi-block copolymers, PEG had no effect in inhibiting aggregation of HEWL or of carboxypeptidase A with the recovery of catalytic activity. At very high polymer:protein ratios (>or=10:1), PEG increased aggregation of heat-denatured HEWL and BSA, consistent with its known properties to promote macromolecular crowding and crystallization of proteins. At a polymer:protein ratio of 2:1, the tetra-block copolymer T1107 was the most effective of the three surfactant copolymers, completely suppressing aggregation of heat-denatured HEWL. At a T1107:BSA ratio of 10:1, the poloxamer suppressed aggregation of heat-denatured BSA by 50% compared to that observed in the absence of the polymer. We showed that the extent of suppression of aggregation of heat-denatured proteins by multi-block surfactant copolymers is dependent on the size of the protein and the copolymer:protein molar ratio. We also concluded that at least one of the tertiary nitrogens in the ethylene-1,2-diamine structural core of the T1107 copolymer is protonated, and that this electrostatic factor underlies its capacity to suppress aggregation of denatured proteins more effectively than nonionic, multi-block poloxamers. These results indicate that amphiphilic, surfactant, multi-block copolymers are efficient as additives to suppress aggregation and to facilitate refolding of denatured proteins in solution. Because of these properties, multi-block, surfactant copolymers are suitable for application to a variety of biotechnological and biomedical problems in which refolding of denatured or misfolded proteins and suppression of aggregation are important objectives.
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PMID:Multi-block poloxamer surfactants suppress aggregation of denatured proteins. 1795 Oct 11

Silica nanofibers were prepared by electrospinning method using PVP/P123 blend polymer solutions. Here, a triblock copolymer (Pluronic P123, EO20PO70EO20, M(av) = 5800) was used as the structure directing agent and polyvinyl pyrrolidone (PVP) as the fiber template. The samples were characterized by scanning electron microscopy (SEM), Fourier Transform Infrared (FT-IR), X-ray diffraction (XRD), TGA (thermal gravimetric analysis), and Brunauer-Emmett-Teller (BET). It was found that the silica nanofibers synthesized in this work had uniform pore structure with high surface area. An average fiber diameter, average pore diameter, and surface area were about 300 nm, 2.7 nm and 607 m2 g(-1). Adsorption equilibrium data of lysozyme on the synthesized silica nanofibers were correlated well with Langmuir equation.
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PMID:Preparation and characterization of electrospun silica nanofibers from PVP/P123 blended polymer solution. 1919 9

In this investigation, novel biodegradable physically crosslinked hydrogel microparticles were developed and evaluated in vitro as potential carriers for sustained pulmonary drug delivery. To facilitate sustained release in the lungs, aerosols must first navigate past efficient aerodynamic filtering to penetrate to the deep lung (requires small particle size) where they must then avoid rapid macrophage clearance (enhanced by large particle size). The strategy suggested in this study to solve this problem is to deliver drug-loaded hydrogel microparticles with aerodynamic characteristics allowing them to be respirable when dry but attain large swollen sizes once deposited on moist lung surfaces to reduce macrophage uptake rates. The microparticles are based on PEG graft copolymerized onto chitosan in combination with Pluronic(R) F-108 and were prepared via cryomilling. The synthesized polymers used in preparation of the microparticles were characterized using FTIR, EA, 2D-XRD, and differential scanning calorimetry (DSC). The microparticles size, morphology, moisture content, and biodegradation rates were investigated. Swelling studies and in vitro drug release profiles were determined. An aerosolization study was conducted and macrophage uptake rates were evaluated against controls. The microparticles showed a respirable fraction of approximately 15% when prepared as dry powders. Enzymatic degradation of microparticles started within the first hour and about 7-41% weights were remaining after 240 h. Microparticles showed sustained release up to 10 and 20 days in the presence and absence of lysozyme, respectively. Preliminary macrophage interaction studies indicate that the developed hydrogel microparticles significantly delayed phagocytosis and may have the potential for sustained drug delivery to the lung.
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PMID:Swellable microparticles as carriers for sustained pulmonary drug delivery. 1996 77


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