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)

The body of work described in this research paper outlines the use of PEO/PCL blends in the production of monolithic matrices for oral drug delivery. Several batches of matrix material were prepared with carvedilol used as the active pharmaceutical ingredient. The matrices were prepared using various extrusion parameters to investigate the effect of screw speed and barrel temperature on the properties of the drug delivery devices. The resultant extrudate was characterised using steady state parallel plate rheometry, differential scanning calorimetry (DSC) and dissolution testing. Higher screw speeds were observed to result in slightly lower matrix melt viscosity when compared with matrices compounded using lower screw speeds. Dissolution testing showed that the incorporation of the hydrophobic PCL polymer into a PEO matrix results in a retarded drug release profile.
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PMID:The significance of variation in extrusion speeds and temperatures on a PEO/PCL blend based matrix for oral drug delivery. 1803 53

Steady-state and time-resolved fluorescence measurements were used to study the relaxation of the microenvironment of hydrophobic probes 6-propionyl-2-(dimethylamino)naphthalene (prodan) and 6-dodecanoyl-2-(dimethylamino)naphthalene (laurdan) in systems containing vesicles formed by the amphiphilic diblock copolymer poly(epsilon-caprolactone)-block-poly(ethylene oxide) (PCL-PEO) and water/tetrahydrofurane (THF) solvent mixtures. It was found that in case of prodan, both steady-state and time-resolved emission spectra were composed of two subspectra corresponding to the emission of prodan molecules located (i) in fairly rigid (effectively viscous) and hydrophobic domains of the vesicles close to the PCL/PEO interface and (ii) in a more polar and less viscous medium (in the bulk solution). The fraction of the emission from the more polar microenvironment increases with increasing content of THF in the system. Laurdan, in contrast to prodan, appeared to be solubilized preferentially in the hydrophobic domains up to 30 vol % of THF content, and its emission spectra changed only due to swelling of hydrophobic PCL domains by added THF. The study shows that the analysis of the time-resolved emission from a probe distributed in two media is, in principle, possible, but it is quite complex and appreciably less accurate, and the relaxation times are ill-defined averages of several processes. The bimodal or shoulder-containing time-resolved spectra have to be decomposed in pertinent time-resolved subspectra and treated separately. Another important result of the study is a piece of knowledge concerning the motion of the probe with respect to the vesicle. In the studied complex system, not only the relaxation of the solvent and reorganization of polymer segments around the fluorescent headgroup of the probe affect the emission but also a lateral motion of the probe with respect to the nanoparticle within the lifetime of the excited state contributes significantly to the relaxation and to the relatively slow time-resolved Stokes shift.
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PMID:Fluorescence study of the solvation of fluorescent probes prodan and laurdan in poly(epsilon-caprolactone)-block-poly(ethylene oxide) vesicles in aqueous solutions with tetrahydrofurane. 1804 37

Supramolecular hydrogels formed through inclusion complexation between high molecular weight poly(ethylene oxide) (PEO) and alpha-cyclodextrin (alpha-CD) showed the most sustained release kinetics in vitro with molecular weight of PEO of 35,000 within 5 days. To improve the sustained release and overcome using high molecular weight PEO, novel supramolecular hydrogels have been prepared by using biodegradable amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-PCL) diblock copolymer instead of PEO. Rheologic studies indicate that the prepared hydrogel is thixotropic and reversible. The in vitro release kinetics of hydrogels has been studied by using fluorescein isothiocyanate labeled dextran (dextran-FITC) as model drug. Compared with that of alpha-CD/PEO supramolecular hydrogels, the sustained release of alpha-CD/PEO-PCL supramolecular hydrogel was increased significantly even if with much lower molecular weight of PEO block. This result indicates incorporating hydrophobic PCL block could reduce the molecular weight of PEO required for long-term drug release system. The sustained release is also dependent on the alpha-CD content in supramolecular hydrogels. Thus, the properties of supramolecular hydrogel can be fine-tuned with different polymer and at different alpha-CD content, opening a wide range of applications.
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PMID:Supramolecular hydrogels based on inclusion complexation between poly(ethylene oxide)-b-poly (epsilon-caprolactone) diblock copolymer and alpha-cyclodextrin and their controlled release property. 1806 62

In this work, the potential in drug nanodelivery of micelles made from poly(epsilon-caprolactone) (PCL) and poly (ethyleneoxide) (PEO) copolymers with triblock and star-diblock architectures was explored. Linear and 4-arm star-shaped PCL macromers with two or four --OH end groups were prepared by ring-opening polymerization of CL and condensed with alpha-methoxy-omega-carboxy-PEO. The resulting amphiphilic copolymers were characterized by (1)H NMR, size exclusion chromatography, and differential scanning calorimetry. Separate PCL and PEO crystalline phases were observed for both copolymers. Copolymers self-assembled in water giving critical association concentrations in the range 0.010-0.023 mg/mL. Micelles with a size of 32-45 nm were prepared by dialysis and characterized for hydrodynamic diameter and surface charge. Their potential as nanocarriers in drug delivery applications was evaluated too. Micelles were nontoxic to both Red blood cells and HeLa cells. Complement activation experiments indicated that micelles can escape the reticuloendothelial system once intravenously injected. Finally, a different uptake on HeLa cells was found for micelles obtained from triblock and star-shaped copolymers.
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PMID:Micelles based on amphiphilic PCL-PEO triblock and star-shaped diblock copolymers: Potential in drug delivery applications. 1818 51

Aligned electrospun scaffolds are promising tools for engineering fibrous musculoskeletal tissues, as they reproduce the mechanical anisotropy of these tissues and can direct ordered neo-tissue formation. However, these scaffolds suffer from a slow cellular infiltration rate, likely due in part to their dense fiber packing. We hypothesized that cell ingress could be expedited in scaffolds by increasing porosity, while at the same time preserving overall scaffold anisotropy. To test this hypothesis, poly(epsilon-caprolactone) (a slow-degrading polyester) and poly(ethylene oxide) (a water-soluble polymer) were co-electrospun from two separate spinnerets to form dual-polymer composite fiber-aligned scaffolds. Adjusting fabrication parameters produced aligned scaffolds with a full range of sacrificial (PEO) fiber contents. Tensile properties of scaffolds were functions of the ratio of PCL to PEO in the composite scaffolds, and were altered in a predictable fashion with removal of the PEO component. When seeded with mesenchymal stem cells (MSCs), increases in the starting sacrificial fraction (and porosity) improved cell infiltration and distribution after three weeks in culture. In pure PCL scaffolds, cells lined the scaffold periphery, while scaffolds containing >50% sacrificial PEO content had cells present throughout the scaffold. These findings indicate that cell infiltration can be expedited in dense fibrous assemblies with the removal of sacrificial fibers. This strategy may enhance in vitro and in vivo formation and maturation of functional constructs for fibrous tissue engineering.
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PMID:The potential to improve cell infiltration in composite fiber-aligned electrospun scaffolds by the selective removal of sacrificial fibers. 1831 38

By sequential ring-opening polymerization of ethylene oxide and epsilon-caprolactone, poly(ethylene oxide) (PEO)-poly(epsilon-caprolactone) (PCL) di-block co-polymers with a phosphoryl choline (PC)-terminated group were synthesized. Using FT-IR, NMR, DSC and SEC, the products were characterized and the results proved the successful synthesis of functionalized di-block co-polymer. After blending the products with polyurethane (PU) and casting the result as film, the PEO segments migrated to the surface of the blend and the PCL segments acted as an anchor to fix the co-polymer on PU matrix, while the PEO segments provided PU the hydrophibility to prevent the fibrinogen adsorption on PU. This specific di-block co-polymer and the method of processing are hoped to be applied in the biomedical field to improve the biocompatibility of polymer materials.
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PMID:Synthesis and characterization of phosphoryl-choline-capped poly(epsilon-caprolactone)-poly(ethylene oxide) di-block co-polymers and its surface modification on polyurethanes. 1831 62

A series of poly(ethylene glycol)-block-poly(epsilon-caprolactone)-block-poly(ethylene glycol) (PEO-PCL-PEO) triblock copolymers were prepared and then used for the investigation of the effects of the ratio of epsilon-caprolactone to poly(ethylene glycol) (i.e., [CL]/[EO]) on the physical properties of water-in-oil-in-water (W(1)/O/W(2)) multiple emulsions containing a model reagent, ascorbic acid-2-glucoside (AA2G). In the synthesis, the [CL]/[EO] was varied from 0.11 to 0.31. The molecular weights and compositions of PEO-PCL-PEO were determined by GPC and (1)H NMR analyses. Thermal behavior and crystal formation were studied by DSC, XRD, FT-IR, and polarized optical microscopy (POM). Aggregate behavior of PEO-PCL-PEO was confirmed by DLS, UV, and (1)H NMR. Morphology and relative stiffness of the W(1)/O/W(2) multiple emulsions in the presence of PEO-PCL-PEO were studied by confocal laser scanning microscopy (CLSM) and rheometer. Variation in the [CL]/[EO] significantly affects the crystalline temperature and spherulite morphology of PEO-PCL-PEO. As the [CL]/[EO] increases, the CMCs of PEO-PCL-PEO decreases and the slope of aggregate size reduction against the copolymer concentration becomes steeper except for the lowest [CL]/[EO] value of PEO-PCL-PEO (i.e., P-222). P-222 significantly increases the viscosity of continuous (W(2)) phase, which implies the copolymer would exist in the W(2) phase. On the other hand, the triblock copolymers with relatively high [CL]/[EO] ratios mainly contribute to the size reduction of multiple emulsions and the formation of a firm wall structure. The particle size of the multiple emulsion decreases and the elastic modulus increased as [CL]/[EO] increases, confirmed by microscopic and rheometric analyses.
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PMID:Synthesis and characterization of PEO-PCL-PEO triblock copolymers: effects of the PCL chain length on the physical property of W(1)/O/W(2) multiple emulsions. 1840 Apr 73

Novel micelle-forming poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) block copolymers bearing doxorubicin (DOX) side groups (PEO-b-P(CL-DOX)) on the PCL block were synthesized. Prepared block copolymers were characterized, assembled to polymeric micellar drug conjugates and assessed for the level of DOX release at pH 7.4 and pH 5.0 using a dialysis membrane to separate released and conjugated drug. The possibility for the degradation of PCL backbone for PEO-b-P(CL-DOX) micelles was investigated using gel permeation chromatography. Micelle-forming DOX conjugate did not show any signs of DOX release at 37 degrees C within 72h of incubation at both pHs, but revealed signs of poly(ester) core degradation at pH 5.0. In further studies, PEO-b-PCL micelles bearing benzyl, carboxyl or DOX groups in the core were also used as micellar nano-containers for the physical encapsulation of DOX, where maximum level of drug-loading and control over the rate of DOX release was achieved by polymeric micelles containing benzyl groups in their core, i.e., PEO-b-poly(alpha-benzylcarboxylate-epsilon-caprolactone) (PEO-b-PBCL) micelles. The in vitro cytotoxicity of chemically conjugated DOX as part of PEO-b-P(CL-DOX) and physically encapsulated DOX in PEO-b-PBCL against B16F10 murine melanoma cells was assessed and compared to that of free DOX. Consistent with the results of in vitro release study, cytotoxicity of micellar PEO-b-P(CL-DOX) conjugate (IC50 of 3.65 microg/mL) was lower than that of free and physically encapsulated DOX in PEO-b-PBCL (IC50 of 0.09 and 3.07 microg/mL, respectively) after 24 h of incubation. After 48 h of incubation, the cytotoxicity of conjugated DOX (IC50 of 0.50 microg/mL) was still lower than the cytotoxicity of free DOX (IC50 of 0.03 microg/mL), but surpassed that of physically encapsulated DOX in PEO-b-PBCL (IC50 of 1.54 microg/mL). The results point to a potential for PEO-b-P(CL-DOX) and PEO-b-PBCL as novel polymeric micellar drug conjugates and nano-containers bearing hydrolyzable cores for DOX delivery.
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PMID:Development of novel polymeric micellar drug conjugates and nano-containers with hydrolyzable core structure for doxorubicin delivery. 1843 May 50

This work describes the development of polymersome-encapsulated hemoglobin (PEH) self-assembled from biodegradable and biocompatible amphiphilic diblock copolymers composed of poly(ethylene oxide) (PEO), poly(caprolactone) (PCL), and poly(lactide) (PLA). In the amphiphilic diblock, PEO functions as the hydrophilic block, while either PCL or PLA can function as the hydrophobic block. PEO, PCL, and PLA are biocompatible polymers, while the last two polymers are biodegradable. PEH dispersions were prepared by extrusion through 100 nm pore radii polycarbonate membranes. In this work, the encapsulation efficiency of human and bovine hemoglobin (hHb and bHb) in polymersomes was adjusted by varying the initial concentration of Hb. This approach yielded Hb loading capacities that were comparable to values in the literature that supported the successful resuscitation of hamsters experiencing hemorrhagic shock. Moreover, the Hb loading capacities of PEHs in this study can also be tailored simply by controlling the diblock copolymer concentration. In this study, typical Hb/diblock copolymer weight ratios ranged 1.2-1.5, with initial Hb concentrations less than 100 mg/mL. The size distribution, Hb encapsulation efficiency, oxygen affinity (P 50), cooperativity coefficient (n), and methemoglobin (metHb) level of these novel PEH dispersions were consistent with values required for efficient oxygen delivery in the systemic circulation. Taken together, our results demonstrate the development of novel PEH dispersions that are both biocompatible and biodegradable. These novel dispersions show very good promise as therapeutic oxygen carriers.
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PMID:Biocompatible and biodegradable polymersome encapsulated hemoglobin: a potential oxygen carrier. 1844 83

A simple and sensitive HPLC method has been developed and validated for the determination of oridonin (ORI) in rabbit plasma. A simple liquid-liquid extraction (LLE) method was applied to extract ORI and the internal standard (IS), isopsoralen, from rabbit plasma. Chromatographic separation of ORI and the IS was achieved with a Kromasil C18 5-mum column (250 mm x 4.6 mm) using methanol-water (50:50, v/v) as mobile phase at a flow rate of 1 mL/min. The ultraviolet (UV) detection wavelength was set at 241 nm. The lower limit of quantification (LLOQ) was 0.02 microg/mL. The calibration curves were linear over a concentration range of 0.02-10 microg/mL. The assay accuracy and precision were within the range of 95.1-113.5% and 5.4-8.6%, respectively. This HPLC method was applied successfully to the pharmacokinetic study of ORI-loaded poly(caprolactone)-poly(ethylene oxide)-poly(caprolactone) copolymer nanoparticles (ORI-PCL-PEO-PCL-NP) in rabbits, given as a single intravenous injection at the dose equivalent to 2mg of ORI/kg, and the pharmacokinetic parameters for ORI were compared with a single intravenous injection of a ORI solution at the same dose.
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PMID:An HPLC method for determination of oridonin in rabbits using isopsoralen as an internal standard and its application to pharmacokinetic studies for oridonin-loaded nanoparticles. 1851 94


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