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)

Various hormone replacement regimens and delivery systems have been developed; however, there is still a need for additional, easily controllable and biocompatible systems. We have developed and characterized biocompatible polycaprolactone-block-poly(ethylene oxide) (PCL-b-PEO) micelles for the delivery of 17beta-estradiol (E2) and investigated their loading and release properties using fluorescence spectroscopy. The micelles are spherical aggregates that range in size from 20 to 40 nm, as determined by both transmission electron microscopy and dynamic light scattering. A high loading efficiency for E2 of up to 96%, as well as a high drug loading capacity of up to 4000 molecules of E2 per micelle (equivalent to 190% (w/w)), is obtainable. In addition, the E2 loading and release can be controlled by modifying the block length of the polycaprolactone core and the initial estradiol concentration. The release of E2 from the micelles showed a biphasic profile under perfect sink conditions: there is an initial burst release, followed by a slow and prolonged release for up to 5 days, until complete release is achieved. The release of E2 from the micelles was shown to be diffusional, as shown by the linearity of the release as a function of the square root of time. Approximate diffusion coefficients of the order of 10(-17) cm2/s were obtained. In vitro and in vivo experiments confirmed that the biological activity of E2 was retained after preparation of the micelles. This micelle carrier could serve as a versatile and efficient nanodelivery system for steroids and other poorly water soluble drugs that require solubilizing agents for delivery.
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PMID:Polycaprolactone-block-poly(ethylene oxide) micelles: a nanodelivery system for 17beta-estradiol. 1632 59

Hydrogels with nanoscale structure were synthesized using amphiphilic poly(epsilon-caprolactone)-poly(ethylene oxide)-poly(epsilon-caprolactone) (PCL-b-PEO-b-PCL) triblock copolymers. Small-angle X-ray scattering (SAXS) studies show that the block copolymers form 30-40 nm structures in aqueous solution and that these patterns are retained, with some increase in length scale, following electron beam cross-linking. Lamellar nanostructures were observed by SAXS and atomic force microscopy (AFM), with SAXS indicating cylindrical structure as the block lengths become more different in length. It is demonstrated through Fourier transform infrared spectroscopy (FTIR), mass loss, and differential scanning calorimetry (DSC) that the PCL can be completely removed by hydrolysis in NaOH(aq) to form porous PEO hydrogels. These hydrogels retain active functional groups following PCL removal that serve as sites for further chemical modification.
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PMID:Synthesis and characterization of PCL-b-PEO-b-PCL-based nanostructured and porous hydrogels. 1647 16

The electrospinning of polymer melts can offer an advantage over solution electrospinning, in the development of layered tissue constructs for tissue engineering. Melt electrospinning does not require a solvent, of which many are cytotoxic in nature, and the use of nonwater soluble polymers allows the collection of fibers on water or onto cells. In this article, melt electrospinning of a blend of PEO-block-PCL with PCL was performed with in vitro cultured fibroblasts as the collection target. The significant parameters governing electrospinning polymer melts were determined before electrospinning directly onto fibroblasts. In general, a high electric field resulted in the most homogeneous and smallest fibers, although it is important that an optimal pump rate to the spinneret needs to be determined for different configurations. Many parameters governing melt electrospinning differ to those reported for solution electrospinning: the pump rate was a magnitude lower and the viscosity a magnitude higher than successful parameters for solution electrospinning. Cell vitality was maintained throughout the electrospinning process. Six days after electrospinning, fibroblasts adhered to the electrospun fibers and appeared to detach from the underlying flat substrate. The morphology of the fibroblasts changed from spread and flat, to long and spindle-shaped as adherence onto the fiber progressed. Therefore, an important step for producing layer-on-layer tissue constructs of cells and polymers in view of scaffold construction for tissue engineering was successfully demonstrated. The process of using cultured cells as the collection target was termed "direct in vitro electrospinning".
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PMID:Direct in vitro electrospinning with polymer melts. 1652

The aim of this work was to design injectable nanocarriers for drug delivery based on PCL-PEO amphiphilic block copolymers with linear ABA triblock and 4-armed (BA)(4) star-diblock architectures (A=PEO, B=PCL). The copolymers were obtained by coupling of a monofunctional -COOH end-capped PEO (M(n)=2.0kDa) with linear or 4-armed star-shaped PCL macromers bearing -OH terminal groups and were characterized by (1)H NMR spectroscopy and size exclusion chromatography. DSC and X-ray diffraction experiments showed that separate crystalline phases of PCL and PEO are present in bulk copolymers. Nanoparticles were produced by nanoprecipitation (NP) and by a new melting-sonication procedure (MS) without the use of toxic solvents, and characterized for size, polydispersity, zeta potential and core-shell structure. Nanoparticles were loaded with all-trans-retinoic acid (atRA) as a model drug and their release features assessed. Results demonstrate that both techniques allow the formation of PEO-coated nanoparticles with a hydrodynamic diameter that is larger for nanoparticles prepared by MS. atRA is released from nanoparticles at controlled rates depending on size, loading and, more important, preparation technique, being release rate faster for MS nanoparticles. Some biorelevant properties of the carrier such as complement activation were finally explored to predict their circulation time after intravenous injection. It is demonstrated that nanoparticles prepared by MS do not activate complement and are of great interest for future in vivo applications.
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PMID:Nanoscopic core-shell drug carriers made of amphiphilic triblock and star-diblock copolymers. 1692 Feb 88

Novel biodegradable and biocompatible poly(epsilon-caprolactone)-graft-poly(ethylene oxide), PCL-g-PEO, copolymers consisting of biocompatible blocks have been synthesized by ring-opening copolymerization of epsilon-caprolactone (epsilon CL) and a poly(ethylene oxide) (PEO) macromonomer, i.e., PEO end-capped by an epsilon-caprolactone unit (gamma PEO.CL). The control is effective on the composition and length of both the hydrophobic polyester backbone and the hydrophilic PEO grafts. The reactivity ratios have been determined by monitoring the copolymer composition in relation to the comonomer conversion. The PCL-g-PEO copolymers have a tapered (gradient) rather than a random structure consistent with r(epsilon)CL = 3.95 and r(gamma)PEO.CL = 0.05. The amphiphilic graft copolymers display surfactant properties similar to those of PEO-b-PCL diblock copolymers of comparable composition and solubility, as supported by CHCl3/water interfacial tension measured by the pendant drop method.
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PMID:Controlled synthesis and interface properties of new amphiphilic PCL-g-PEO copolymers. 1692 23

Micelles and quantum dots have been used as experimental drug delivery systems and imaging tools both in vitro and in vivo. Investigations of their fate at the subcellular level require different surface-core modifications. Among the most common modifications are those with fluorescent probes, dense-core metals or radionucleids. Cellular fate of several fluorescent probes incorporated into poly(caprolactone)-b-copolymer micelles (PCL-b-PEO) was followed by confocal microscopy, and colloidal gold incorporated in poly 4-vinyl pyridine-PEO micelles were developed to explore micelle fate by electron microscopy. More recently, we have examined quantum dots (QDs) as the next-generation-labels for cells and nanoparticulate drug carriers amenable both to confocal and electron microscopic analyses. Effects of QDs at the cellular and subcellular levels and their integrity were studied. Results from different studies suggest that size, charge and surface manipulations of QDs may play a role in their subcellular distribution. Examples of pharmacological agents incorporated into block copolymer micelles, administered or attached to QD surfaces show how the final biological outcome (e.g. cell death, proliferation or differentiation) depends on physical properties of these nanoparticles.
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PMID:Fate of micelles and quantum dots in cells. 1702 43

Self-assembly of poly(ethylene oxide)-block-poly(epsilon-caprolactone) five-arm stars (PEO-b-PCL) was studied at the air/water (A/W) interface. The block copolymers consist of a hydrophilic PEO core with hydrophobic PCL chains at the star periphery. All the polymers have the same number of ethylene oxide repeat units (9 per arm), and the number of epsilon-caprolactone repeat units ranges from 0 to 18 per arm. The Langmuir monolayers were analyzed by surface pressure/mean molecular area isotherms, compression-expansion hysteresis experiments, and isobaric relaxation measurements, and the Langmuir-Blodgett (LB) films' morphologies were investigated by atomic force microscopy (AFM). PCL homopolymers crystallize directly at the A/W interface in a narrow surface pressure range (11-15 mN/m). In the same pressure region, the star-shaped block copolymers undergo a phase transition corresponding to the collapse and the crystallization of the PCL chains as shown by the presence of a pseudoplateau in the isotherms. The LB films were prepared by transferring the Langmuir monolayers onto mica substrates at various surface pressures. AFM imaging confirmed the formation of PCL crystals in the LB monolayers of the PCL homopolymers and of the copolymers, but also showed that the PCL segments can undergo additional crystallization after monolayer transfer during water evaporation. The PCL crystal morphologies were also strongly influenced by the surface pressure and by the PEO segments.
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PMID:Langmuir and Langmuir-Blodgett films of poly(ethylene oxide)-b-poly(epsilon-caprolactone) star-shaped block copolymers. 1704 41

We investigated material models for a polymeric scaffold used for bone. The material was made by co-extruding poly(epsilon-caprolactone) (PCL), a biodegradable polyester, and poly(ethylene oxide) (PEO). The water soluble PEO was removed resulting in a porous scaffold. The stress-strain curve in compression was fit with a phenomenological model in hyperbolic form. This material model will be useful for designers for quasi-static analysis as it provides a simple form that can easily be used in finite element models. The ASTM D-1621 standard recommends using a secant modulus based on 10% strain. The resulting modulus has a smaller scatter in its value compared with the coefficients of the hyperbolic model, and it is therefore easier to compare differences in material processing and ensure quality of the scaffold. A prediction of the small-strain elastic modulus was constructed from images of the microstructure. Each pixel of the micrographs was represented with a brick finite element and assigned the Young's modulus of bulk PCL or a value of 0 for a pore. A compressive strain was imposed on the model and the resulting stresses were calculated. The elastic constants of the scaffold were then computed with Hooke's law for a linear-elastic isotropic material. The model was able to predict the small-strain elastic modulus measured in the experiments to within one standard deviation. Thus, by knowing the microstructure of the scaffold, its bulk properties can be predicted from the material properties of the constituents.
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PMID:Material model measurements and predictions for a random pore poly(epsilon-caprolactone) scaffold. 1710 97

The crystallization behavior and morphology of the crystalline-crystalline poly(ethylene oxide)-poly(epsilon-caprolactone) diblock copolymer (PEO-b-PCL) was studied by differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), Fourier transform infrared spectroscopy (FTIR), small-angle X-ray scattering (SAXS), and hot-stage polarized optical microscope (POM). The mutual effects between the PEO and PCL blocks were significant, leading to the obvious composition dependence of the crystallization behavior and morphology of PEO-b-PCL. In this study, the PEO block length was fixed (Mn = 5000) and the weight ratio of PCL/PEO was tailored by changing the PCL block length. Both blocks could crystallize in PEO-b-PCL with the PCL weight fraction (WFPCL) of 0.23-0.87. For the sample with the WFPCL of 0.36 or less, the PEO block crystallized first, resulting in the obvious confinement of the PCL block and vice versa for the sample with WFPCL of 0.43 or more. With increasing WFPCL, the crystallinity of PEO reduced continuously while the variation of the PCL crystallinity exhibited a maximum. The long period of PEO-b-PCL increased with increasing WFPCL from 0.16 to 0.50 but then decreased with the further increase of WFPCL due to the interaction of the respective variation of the thicknesses of the PEO and PCL crystalline lamellae. Only the PEO spherulites were observed in samples with WFPCL of 0.16-0.36 by POM, in contrast to only the PCL spherulites in samples with WFPCL of 0.56-0.87. For samples with WFPCL of 0.43 and 0.50, a unique concentric spherulite was observed. The morphology of the inner and outer portions of the concentric spherulites was determined by the PCL and PEO spherulites, respectively. The growth rate of the PEO spherulites reduced rapidly with increasing WFPCL from 0 to 0.50. However, when increasing WFPCL from 0.43 to 0.87, the variation of the growth rate of the PCL spherulites exhibited a maximum rather than a monotonic change.
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PMID:Composition dependence of the crystallization behavior and morphology of the poly(ethylene oxide)-poly(epsilon-caprolactone) diblock copolymer. 1715 78

The morphology of a highly asymmetric double crystallizable poly(epsilon-caprolactone-b-ethylene oxide) (PCL-b-PEO) block copolymer has been studied with in situ simultaneously small and wide-angle x-ray scattering as well as atomic force microscopy. The molecular masses Mn of the PCL and PEO blocks are 24,000 and 5800, respectively. X-ray scattering and rheological measurements indicate that no microphase separation occurs in the melt. Decreasing the temperature simultaneously triggers off a crystallization of PCL and microphase separation between the PCL and PEO blocks. Coupling and competition between microphase separation and crystallization results in a morphology of PEO spheres surrounded by PCL partially crystallized in lamella. Further decreasing temperature induces the crystallization of PEO spheres, which have a preferred orientation due to the confinements from hard PCL crystalline lamella and from soft amorphous PCL segments in different sides. The final morphology of this highly asymmetric block copolymer is similar to the granular morphology reported for syndiotactic polypropylene and other (co-) polymers. This implies a similar underlying mechanism of coupling and competition of various phase transitions, which is worth further exploration.
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PMID:Morphology of a highly asymmetric double crystallizable poly(epsilon-caprolactone-b-ethylene oxide) block copolymer. 1722 70


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