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:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the field of tissue engineering new polymers are needed to fabricate scaffolds with specific properties depending on the targeted tissue. This work aimed at designing and developing a 3D scaffold with variable mechanical strength, fully interconnected porous network, controllable hydrophilicity and degradability. For this, a desktop-robot-based melt-extrusion rapid prototyping technique was applied to a novel tri-block co-polymer, namely poly(ethylene glycol)-block-poly(epsilon-caprolactone)-block-poly(DL-lactide), PEG-PCL-P(DL)LA. This co-polymer was melted by electrical heating and directly extruded out using computer-controlled rapid prototyping by means of compressed purified air to build porous scaffolds. Various lay-down patterns (0/30/60/90/120/150 degrees, 0/45/90/135 degrees, 0/60/120 degrees and 0/90 degrees) were produced by using appropriate positioning of the robotic control system. Scanning electron microscopy and micro-computed tomography were used to show that 3D scaffold architectures were honeycomb-like with completely interconnected and controlled channel characteristics. Compression tests were performed and the data obtained agreed well with the typical behavior of a porous material undergoing deformation. Preliminary cell response to the as-fabricated scaffolds has been studied with primary human fibroblasts. The results demonstrated the suitability of the process and the cell biocompatibility of the polymer, two important properties among the many required for effective clinical use and efficient tissue-engineering scaffolding.
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PMID:Fabrication using a rapid prototyping system and in vitro characterization of PEG-PCL-PLA scaffolds for tissue engineering. 1636 39

The crystallization behaviors of the poly(ethylene glycol)-poly(epsilon-caprolactone) diblock copolymer with the PEG weight fraction of 0.50 (PEG(50)-PCL(50)) was studied by DSC, WAXD, SAXS, and FTIR. A superposed melting point at 58.5 degrees C and a superposed crystallization temperature at 35.4 degrees C were obtained from the DSC profiles running at 10 degrees C/min, whereas the temperature-dependent FTIR measurements during cooling from the melt at 0.2 degrees C/min showed that the PCL crystals formed starting at 48 degrees C while the PEG crystals started at 45 degrees C. The PEG and PCL blocks of the copolymer crystallized separately and formed alternating lamella regions according to the WAXD and SAXS results. The crystal growth of the diblock copolymer was observed by polarized optical microscope (POM). An interesting morphology of the concentric spherulites developed through a unique crystallization behavior. The concentric spherulites were analyzed by in situ microbeam FTIR, and it was determined that the morphologies of the inner and outer portions were mainly determined by the PCL and PEG spherulites, respectively. However, the compositions of the inner and outer portions were equal in the analysis by microbeam FTIR.
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PMID:Formation of a unique crystal morphology for the poly(ethylene glycol)-poly(epsilon-caprolactone) diblock copolymer. 1639 22

This study presents a method for the design of novel composite core-shell nanoparticles able to encapsulate busulfan, a crystalline drug. They were obtained by co-precipitation of mixtures of poly(isobutylcyanoacrylate) (PIBCA) and of a diblock copolymer, poly(epsilon-caprolactone)-poly(ethylene glycol) (PCL-PEG), in different mass ratios. The nanoparticle size, morphology and surface charge were assessed. The chemical composition of the top layers was determined by X-ray photo-electron spectroscopy (XPS). (3)H-labelled busulfan was used in order to determine the drug loading efficiency and the in vitro drug release by liquid scintillation counting. Physico-chemical techniques such as Zeta potential determination and XPS analysis provided evidence about a preferential surface distribution of the PCL-PEG polymer. Therefore, composite nanoparticles have a "core-shell"-type structure, where the "core" is essentially formed by the PIBCA polymer and the "shell" by the PCL-PEG copolymer. The use of PIBCA to form the core of the nanoparticles leads to a 2-4 fold drug loading increase, in comparison to the single PCL-PEG nanoparticles. In addition, the complement activation results showed a significant difference between the composite nanoparticles and the single PIBCA nanoparticles, thus demonstrating that PEG at the surface of the nanoparticles reduced the complement consumption. The PIBCA:PCL-PEG composite nanoparticles prepared using the new co-precipitation method here described represent an original approach for busulfan administration.
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PMID:Novel composite core-shell nanoparticles as busulfan carriers. 1648 4

Cisplatin is a potent anticancer drug with low solubility in water. A new type of highly stable polymer micelles, namely core-surface-crosslinked nanoparticles (SCNPs) made from amphiphilic brush copolymers, were evaluated as the carrier of cisplatin. Cisplatin could be loaded in the SCNPs with poly(epsilon-caprolactone) (PCL) cores and hydrophilic poly(ethylene glycol) (PEG) or poly[2-(N,N-dimethylamino)ethyl methacrylate] (PDMA) shells with high loading efficiency (approximately 90%). In vitro cellular uptake experiments indicated that both SCNPs could be easily taken up by SKOV-3 ovarian cancer cells. Both cell proliferation assay and IC50 measurements indicated that cisplatin encapsulated in the SCNPs had much enhanced cytotoxicity to the cancer cells compared to free cisplatin. The positive charges on the PCL/PDMA SCNPs promoted the cellular internalization of the nanoparticles, resulting in higher cytotoxicity of cisplatin in these SCNPs. The IC50 of the cisplatin encapsulated in PCL/PDMA SCNPs was as low as 0.01 microg/mL, lower than that of cisplatin in PCL/PEG SCNPs and free cisplatin.
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PMID:Highly stable core-surface-crosslinked nanoparticles as cisplatin carriers for cancer chemotherapy. 1649 89

Although 2,4,6-trinitrotoluene (TNT) has been found to uncouple nitric oxide synthase (NOS), thereby leading to reactive oxygen species (ROS), cellular response against TNT still remains unclear. Exposure of bovine aortic endothelial cells (BAECs) to TNT (100 microM) resulted in serine 1179 phosphorylation of endothelial NOS (eNOS). With specific inhibitors (wortmannin and LY294002), we found that PI3K/Akt signaling participated in the eNOS phosphorylation caused by TNT, whereas the ERK pathway did not. ROS were generated following exposure of BAECs to TNT. However, TNT-mediated phosphorylation of either eNOS or Akt was drastically blocked by NAC and PEG-CAT. Interestingly, pretreatment with apocynin, a specific inhibitor for NADPH oxidase, diminished the phosphorylation of eNOS and Akt. These results suggest that TNT affects NADPH oxidase, thereby generating hydrogen peroxide, which is capable of activating PI3K/Akt signaling associated with eNOS Ser 1179 phosphorylation.
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PMID:Serine 1179 phosphorylation of endothelial nitric oxide synthase caused by 2,4,6-trinitrotoluene through PI3K/Akt signaling in endothelial cells. 1651 56

The objective of these investigations was to test the hypothesis that a rapid cytoplasmic release profile from nanoparticles would potentiate the anticancer activity of cisplatin. Cisplatin-loaded nanoparticles with pH-responsive poly[2-(N,N-diethylamino)ethyl methacrylate] (PDEA) cores were synthesized from PDEA-block-poly(ethylene glycol) (PDEA-PEG) copolymer by using a solvent-displacement (acetone-water) method. Nanoparticles with pH-nonresponsive poly(epsilon-caprolactone) (PCL) cores made from PCL-block-PEG (PCL-PEG) were used for comparison. Nanoparticle sizes, zeta potentials, drug-loading capacities, and pH responsiveness were characterized. The cellular uptakes and localization in lysosomes were visualized by using confocal fluorescence microscopy. Cytostatic effects of free and encapsulated cis-diammineplatinum(II) dichloride (cisplatin) toward human SKOV-3 epithelial ovarian cancer cells were estimated by using the MTT assay. Intraperitoneal tumor responses to cisplatin and cisplatin/PDEA-PEG were evaluated in athymic mice at 4-6 weeks postinoculation of SKOV-3 cells. PDEA-PEG nanoparticles dissolved at pH < 6 and rapidly internalized and transferred to lysosomes; it therefore was predicted that the PDEA nanoparticles would rapidly release cisplatin into cytoplasm upon integration into acidic lysosomes and thereby overwhelm the chemoresistant properties of SKOV-3 cells. Indeed, relative proportions of viable cells were diminished to a greater extent by exposure in vitro to fast-releasing nanoparticles compared to slow-releasing nanoparticles or an equivalent dose of free cisplatin. Incidences of cellular pyknosis (a morphological indicator of apoptosis) were most evident within intestinal/mesentery tumors of mice treated with cisplatin/PDEA-PEG; tumor burdens were correspondingly reduced.
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PMID:Anticancer efficacies of cisplatin-releasing pH-responsive nanoparticles. 1652 20

As an aim toward developing biologically mimetic and functional nanofiber-based tissue engineering scaffolds, we demonstrated the encapsulation of a model protein, fluorescein isothiocyanate-conjugated bovine serum albumin (fitcBSA), along with a water-soluble polymer, poly(ethylene glycol) (PEG), within the biodegradable poly(epsilon-caprolactone) (PCL) nanofibers using a coaxial electrospinning technique. By variation of the inner flow rates from 0.2 to 0.6 mL/h with a constant outer flow rate of 1.8 mL/h, fitcBSA loadings of 0.85-2.17 mg/g of nanofibrous membranes were prepared. Variation of flow rates also resulted in increases of fiber sizes from ca. 270 nm to 380 nm. The encapsulation of fitcBSA/PEG within PCL was subsequently characterized by laser confocal scanning microscopy, transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) analysis. In vitro release studies were conducted to evaluate sustained release potential of the core-sheath-structured composite nanofiber PCL-r-fitcBSA/PEG. As a negative control, composite nanofiber PCL/fitcBSA/PEG blend was prepared from a normal electrospinning method. It was found that core-sheath nanofibers PCL-r-fitcBSA/PEG pronouncedly alleviated the initial burst release for higher protein loading and gave better sustainability compared to that of PCL/fitcBSA/PEG nanofibers. The present study would provide a basis for further design and optimization of processing conditions to control the nanostructure of core-sheath composite nanofibers and ultimately achieve desired release kinetics of bioactive proteins (e.g., growth factors) for practical tissue engineering applications.
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PMID:Coaxial electrospinning of (fluorescein isothiocyanate-conjugated bovine serum albumin)-encapsulated poly(epsilon-caprolactone) nanofibers for sustained release. 1660 20

Two types of nanoparticles containing pGL3-Control (plasmid DNA) were prepared using nonionic amphiphlic block copolymers and ionic amphiphilic block copolymers containing a terminal cationic group to investigate the effect of charge on the vehicle properties for systemic gene delivery. Methoxy poly(ethylene glycol) (MPEG)/poly(epsilon-caprolactone) (PCL) diblock copolymers were synthesized by the ring-opening polymerizatrion of epsilon-caprolactone in the presence of a catalyst-free MPEG homopolymer. The hydroxy groups of MPEG/PCL block copolymer were then modified into an amine group to synthesize an amine-terminated MPEG/PCL diblock copolymer (AMPEG/PCL). DNA was incorporated into the polymeric nanoparticles by physical entrapment and electrostatic interaction. All nanoparticle samples exhibited spherical structures and although their sizes increased slightly after DNA-loading, they remained less than 160 nm. The AMPEG/PCL nanoparticles exhibited smaller particle sizes than the MPEG/PCL nanoparticles of the same molecular weight after DNA-loading. The optimum mixing ratio of MPEG/PCL and AMPEG/PCL copolymers to DNA ranged from 4:1 to 1:2 depending on the molecular weight of the block copolymer, the composition of MPEG and PCL and terminal amine group. Based on in vitro cytotoxicity tests, the DNA-loaded MPEG/PCL and AMPEG/PCL nanoparticles did not induce any remarkable cytotoxicity against normal human fibroblasts. Transfection efficiencies of DNA-loaded nanoparticles were improved about 3.4 - 12.9 times under serum conditions.
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PMID:Poly(ethylene glycol)/poly(epsilon-caprolactone) diblock copolymeric nanoparticles for non-viral gene delivery: the role of charge group and molecular weight in particle formation, cytotoxicity and transfection. 1675 Feb 79

Amphiphilic hydrogels composed of aliphatic polyesters and poly(ethylene glycol) have potential applications in drug delivery, tissue engineering and other biomedical devices due to their advantageous biological properties, biocompatibility and biodegradability. However, they also exhibit some shortcomings in terms of their reactivity, swelling and mechanical properties. To address these limitations, new semi-interpenetrating network (semi-IPN) hydrogels based on poly(ethylene glycol)-co-poly(epsilon-caprolactone) (PEG-PCL) diacrylate macromer and hydroxypropyl guar gum (HPGG) were prepared by a low intensity ultraviolet (UV) light irradiation method, and characterized by FT-IR, DSC and WAXD analysis. Their properties were evaluated by investigating the swelling kinetics, dynamic mechanical rheology and the release behavior for bovine serum albumin (BSA). It was found that the introduction of the semi-IPN structure and HPGG decreased the crystallinity of PEG segments in the hydrogel, and improved the swelling and mechanical properties of the hydrogel, as well as lowered the release percentage of BSA from the hydrogel. Such hydrogel materials may have more advantages as a potentially interesting platform for the design of medical devices.The elastic modulus (G') and viscous modulus (G'') as a function of frequency for various hydrogel samples.
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PMID:New semi-interpenetrating network hydrogels: synthesis, characterization and properties. 1676 Dec 76

On the basis of the synthesis of water-soluble poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) block copolymers, the supramolecular hydrogels were fabricated rapidly in aqueous solutions by their inclusion complexation with alpha-cyclodextrin. X-ray diffraction (XRD) analyses confirmed the supramolecular self-assemblies of alpha-cyclodextrin threaded onto amphiphilic PCL-PEG-PCL block copolymers. The resulting hydrogels display a high degree of elasticity, with the storage modulus (G') greater than the loss modulus (G'') over the entire range of frequency. Moreover, their viscosity greatly diminished as they were sheared. By controlling the molecular weight of the PEG component in the block copolymers and the content of the block copolymer, their rheological properties could be modulated. Such hydrogel materials have the potential to be used as tissue engineered scaffolds, biosensors in the human body, and carriers for controlled drug delivery.
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PMID:Supramolecular hydrogels induced rapidly by inclusion complexation of poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) block copolymers with alpha-cyclodextrin in aqueous solutions. 1680 May 42


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