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The phase behavior of poly(ethylene glycol) grafted liposomes (PEG-liposomes) was investigated by differential scanning calorimetry (DSC), dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM). PEG-liposomes were prepared from mixtures of dipalmitoyl phosphatidylcholine (DPPC) and distearoyl phosphatidylethanolamine with a covalently attached PEG molecular weight of 2000 (DSPE-PEG2000). From the results of DLS measurements, the coexistence of PEG-liposomes and small molecular assemblies were confirmed at mole fractions of DSPE-PEG2000 above about 0.1. Moreover, it was confirmed that small molecular assemblies were disk micelles by cryo-TEM. However, the phase transition enthalpies of PEG-liposomes were hardly changed according to the DSC measurement, though the mole fraction of the PEG lipid increased. From these results, it was suggested that the phase transition enthalpies hardly changed despite mixed micelles being formed because the bilayer structure of the disk micelle maintains high cooperativity between the DPPC molecules.
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PMID:Calorimetry and cryo-transmission electron microscopic studies of PEG2000-grafted liposomes. 1659 66

Porous poly(ethylene glycol) terephthalate:poly (butylene terephthalate) (PEGT:PBT) scaffolds with high PEG molecular weight (1000 g/mole) and PEGT content (60%) were fabricated using two different processes-paraffin templating and compression molding-for cartilage engineering applications. This polymer composition has previously been shown to enable chondrocyte adhesion and maintain differentiated phenotype in 2D monolayer culture. The influence of 3D polymer scaffold processing on the formation of cartilaginous tissue was studied by seeding primary immature bovine chondrocytes within cylindrical scaffolds in mixed flask reactors for 3 days, followed by cultivation in culture plates for a total of 10 or 24 days. Tissue-polymer constructs were evaluated morphologically by SEM and histology, and quantitatively for cellularity, total collagen, and glycosaminoglycan content, all of which remained statistically equivalent for each time point tested, irrespective of fabrication method. These data demonstrate that the polymers engineered for this study were able to support chondrogenesis independent of scaffold fabrication process, with the influence of pore architecture lessened by the highly hydrated scaffold microenvironments induced by high PEG content.
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PMID:Evaluation of chondrogenesis within PEGT: PBT scaffolds with high PEG content. 1688 18

New amine-groups containing tri-block copolymers and micelles that consisting of poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCL-b-COS-b-PEG, PCP), were synthesized, characterized, and evaluated for delivering doxorubicin (DOX) with or without crosslinked amine groups by genipin. The characteristics of the PCP copolymers of Fourier-transform infrared spectrometry (FT-IR) verify the amine and ester groups of the COS and the PCL of the copolymers, respectively. 1H nuclear magnetic resonance (1H NMR) spectra verify the structures of the PCP copolymers consisting two PCL and PEG polymers reacted onto the COS block. In addition, gel permeation chromatography (GPC) determines the number average molecular weight of the tri-block copolymers (Mn) of approximately 11340 Da/mole. The PCP copolymers can self-assemble to form polymeric micelles at the critical micelle concentration (CMC) of 1.0 microM as determined by the UV-VIS absorption spectra. The mean diameter of the PCP micelles is 90 nm, as determined using a dynamic light-scattering (DLS) analyzer. Moreover, the zeta potentials of PCP micelles change from neutral to cationic state when pH of suspension mediums varied from 7.4 to 3.0. For evaluating delivery characteristics of hydrophobic DOX, it was loaded into PCP micelles with or without crosslinked by genipin. The burst release and release period of DOX for the crosslinked micelles are significantly reduced (P < 0.003, n = 3, for pH = 7.4) and sustained (e.g., 8 days), respectively, than those non-crosslinked ones (e.g., 4 days). In conclusion, new tri-block amine groups containing PCP copolymers are synthesized that can self-assemble as PCP micelles. After post-crosslinked amine groups of DOX loaded the micelles, they can effectively reduce the burst release and sustain the release of DOX at different pH dissolution mediums. Further applications of PCP copolymers and micelles for drug delivery can be explored in future.
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PMID:Characterizing poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCP) copolymer micelles for doxorubicin (DOX) delivery: effects of crosslinked of amine groups. 1704 97

Therapeutic strategies based on cell and tissue engineering can be advanced by developing material substrates that effectively interrogate the biological compartment, with or without the complimentary local release of growth factors. Poly(ether ester) segmented copolymers were engineered as model material systems to elucidate the interfacial molecular events that govern the function of adhered cells. Surface chemistry was modulated by varying poly(ethylene glycol) (PEG) length and mole fraction with poly(butylene terephthalate) (PBT), leading to differential competitive protein adsorption of fibronectin and vitronectin from serum and consequently to different cell attachment modes. Adhesion within the hydrogel-like milieu of longer surface PEG was mediated via binding to the CD44 transmembrane receptor, rather than the RGD-integrin mechanism, whereas greater substrate-bound fibronectin resulted in cell adhesion via integrins. These adhesion modalities differentially impacted morphological cell phenotype (spread or spheroid) and the subsequent expression of mRNA transcripts (collagen types II, I) characteristic of phenotypically differentiated or dedifferentiated chondrocytes, respectively. These results demonstrate that materials can be designed to directly elicit the membrane bound receptor apparatus desired for downstream cellular response, without requiring exogenous biological growth factors to enable differentiated potential.
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PMID:Modulation of chondrocyte phenotype for tissue engineering by designing the biologic-polymer carrier interface. 1709 26

The aim of this study was to discuss a case of an acute, hemorrhagic, overgrowing vaginal inflammation caused by Streptococcus agalacitae. Intravaginal globules based on methylcellulose and gelatin, containing a lactic acid and chitosan complex in mole relation 1:1 to 4:1 and, in succesion, an addition of hydrophilisating substances like: PEG-200, propylene-1,2 glycol or glycerol, were applied in the treatment process. The technology was invented in Fac. of pharmacy. Dep. of Pharmaceutical Technology, Wroclaw Medical Univ, Poland (recipe patent-protected).
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PMID:[Acute, hemorrhagic, overgrowing vaginal inflammation caused by Streptococcus agalacitae--case study]. 1721 13

Gold nanoparticles have shown great promise as therapeutics, therapeutic delivery vectors, and intracellular imaging agents. For many biomedical applications, selective cell and nuclear targeting are desirable, and these remain a significant practical challenge in the use of nanoparticles in vivo. This challenge is being addressed by the incorporation of cell-targeting peptides or antibodies onto the nanoparticle surface, modifications that frequently compromise nanoparticle stability in high ionic strength biological media. We describe herein the assembly of poly(ethylene glycol) (PEG) and mixed peptide/PEG monolayers on gold nanoparticle surfaces. The stability of the resulting bioconjugates in high ionic strength media was characterized as a function of nanoparticle size, PEG length, and monolayer composition. In total, three different thiol-modified PEGs (average molecular weight (MW), 900, 1500, and 5000 g mol-1), four particle diameters (10, 20, 30, and 60 nm), and two cell-targeting peptides were explored. We found that nanoparticle stability increased with increasing PEG length, decreasing nanoparticle diameter, and increasing PEG mole fraction. The order of assembly also played a role in nanoparticle stability. Mixed monolayers prepared via the sequential addition of PEG followed by peptide were more stable than particles prepared via simultaneous co-adsorption. Finally, the ability of nanoparticles modified with mixed PEG/RME (RME = receptor-mediated endocytosis) peptide monolayers to target the cytoplasm of HeLa cells was quantified using inductively coupled plasma optical emission spectrometry (ICP-OES). Although it was anticipated that the MW 5000 g mol-1 PEG would sterically block peptides from access to the cell membrane compared to the MW 900 PEG, nanoparticles modified with mixed peptide/PEG 5000 monolayers were internalized as efficiently as nanoparticles containing mixed peptide/PEG 900 monolayers. These studies can provide useful cues in the assembly of stable peptide/gold nanoparticle bioconjugates capable of being internalized into cells.
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PMID:Synthesis, stability, and cellular internalization of gold nanoparticles containing mixed peptide-poly(ethylene glycol) monolayers. 1728 7

Modified silica-polyethylene glycol xerogels were prepared by the sol-gel method to explore the possibilities of using these polymers as drug delivery systems. The synthesis was performed at room temperature and under atmospheric pressure using tetraethylorthosilicate (TEOS) as a precursor, low-molecular polyethylene-glycol (600) as a modifier, and acetic acid as a catalyst. The composition in a mole ratio of the initial sols corresponds to TEOS:H(2)O:EtOH:CH(3)COOH:PEG = 1:4:6:0.005:0.147. Diclofenac diethyloammonium was used as a model drug and encapsulated in predoping sol-gel process. After 5 days of gelation time of matrices at room temperature two different forms of xerogels were obtained: monolithic form of pellet and cracked, irregular-shaped of particles. The rate of release from the both forms of xerogels was controlled by the rate of diffusion of the drug through the pores. The dissolution testing for the loaded irregular-shaped xerogels showed an initial burst release followed by sustained release. The degradation of the PEG/silica xerogels followed a zero-order kinetics.
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PMID:Silica-polyethylene glycol matrix synthesis by sol-gel method and evaluation for diclofenac diethyloammonium release. 1745 32

There is a huge clinical demand for Human Serum Albumin (HSA), with a world market of approximately $1.5B/year. Concern over prion and viral transmission in the blood supply has led to a need for safer substitutes and offers the opportunity for development of materials with enhanced properties over the presently available plasma expanders. We report here the synthesis and testing of a new synthetic plasma expander that can replace not only the osmotic and volume expansion properties of HSA but, uniquely, its binding and transport properties. We have synthesized several hyperbranched polyglycerols derivatized with hydrophobic groups and short poly(ethylene glycol) (PEG) chains. The hydrophobic groups provide regions for binding fatty acids and other hydrophobic materials while PEG imparts the necessary protection from host defense systems and enhances circulation longevity. These polymers, being hyperbranched, have only a small effect on plasma viscosity. We have shown in vitro that our materials bind 2-3 moles palmitic acid per mole, do not activate the platelet, coagulation or complement systems and do not cause red cell aggregation. In mice these materials are non-toxic with circulation half-lives as high as 34h, controllable by manipulating the molecular weight and the degree of PEG derivatization.
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PMID:Hydrophobically derivatized hyperbranched polyglycerol as a human serum albumin substitute. 1819 12

The knowledge of the solubility of PEG 1500 as well as the swelling and melting point variation in supercritical CO(2) in a relatively high-pressure range is a necessary prerequisite to set-up pharmaceutical processes dealing with the polymer in the molten state. Experiments carried out in a pressurized view cell indicated that the PEG 1500 progressively decreases its melting point and increases its volume as a consequence of the absorption of the CO(2). The melting point depression was pronounced (from 46 to 28 degrees C) up to 8.7 MPa. Thereafter a constant value was attained. Analogously, under CO(2) the polymer increased its volume (about 34%) until 10 MPa; after this pressure, the polymer volume no longer increased. PEG 1500 showed solubility in SC-CO(2) at 35 and 55 degrees C in the 10-40 MPa range in the order of 10(-6)mole fraction. An empirical model based on solubility parameters was used to fit the experimental data and to predict the maximum concentration achievable by the polymer in the dense gas, as well as to quantify the polymer concentration at low pressures where the experimental determination may be extremely difficult.
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PMID:Swelling, melting point reduction and solubility of PEG 1500 in supercritical CO2. 1829 90

Photopolymerizable hydrogels have been investigated extensively for biomedical applications, specifically in the area of tissue engineering. While fabrication approaches have shown promise in designing hydrogel scaffolds that guide cell function, the ability to spatially control localization in three-dimensions has been limited. We have developed a method for generating two-dimensional and three-dimensional (3D) patterns within multilayered poly(ethylene glycol) diacrylate (PEG-DA) hydrogels. Covalently attached hydrogel layers are formed using precursor solutions with a 10:1 mole ratio of PEG-DA to PEG-aminoacrylate (Acr-PEG-NH2). Upon illumination of the precursor with visible light (wavelength = 514 nm), a hydrogel layer forms with pendant amine groups induced by the presence of Acr-PEG-NH2 macromer. Pendant amine groups are further functionalized with free carboxyl groups present on the visible light photoinitiator eosin, allowing for the formation of subsequent hydrogel layers. Using noncontact photolithography, the prepolymer solution is polymerized through a photomask, resulting in hydrogel structures with distinct pattern formation in each layer. Unreacted regions immobilized with eosin can be subsequently filled with a different PEG hydrogel. The technique presented shows a great potential for tissue engineering applications, for biosensors, and in the formation of cell and protein patterning for biotechnology.
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PMID:Three-dimensional pattering of poly (ethylene Glycol) hydrogels through surface-initiated photopolymerization. 1847 Oct 86


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