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)

PCL/PEO copolymers with different compositions were obtained from ring opening polymerization of epsilon-caprolactone in the presence of ethylene oxide and characterized by various analytical techniques. Data collected from DSC and X-ray diffractometry suggested that the copolymer chains possess a blocky structure, leading to both PCL and PEO-type crystalline structures. Hydrolytic degradation of these copolymers was carried out in a pH=10.6 carbonate buffer solution at 37 degrees C. Comparison was made with a PCL homopolymer and a PCL/PEG blend which had the same gross composition as one of the copolymers. The results showed that the presence of PEO sequences considerably enhanced the hydrophilicity of the copolymers as compared with PCL homopolymer. Nevertheless, the degradability of PCL chains was not enhanced due to the phase separation between the two components. These materials should be of great interest for biomedical uses such as matrices for sustained drug delivery because of the presence of both hydrophilic and hydrophobic microdomains.
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PMID:Hydrolytic degradation of PCL/PEO copolymers in alkaline media. 1534 37

"Stealth" nanoparticles made from polymer micelles have been widely explored as drug carriers for targeted drug delivery. High stability (i.e., low critical micelle concentration (CMC)) is required for their intravenous applications. Herein, we present a "core-surface cross-linking" concept to greatly enhance nanoparticle's stability: amphiphilic brush copolymers form core-surface cross-linked micelles (nanoparticles) (SCNs). The amphiphilic brush copolymers consisted of hydrophobic poly(epsilon-caprolactone) (PCL) and hydrophilic poly(ethylene glycol) (PEG) or poly(2-(N,N-dimethylamino)ethyl methacrylate) (PDMA) chains were synthesized by macromonomer copolymerization method and used to demonstrate this concept. The resulting SCNs were about 100 times more stable than micelles from corresponding amphiphilic block copolymers. The size and surface properties of the SCNs could be easily tailored by the copolymer's compositions.
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PMID:Enhanced stability of core-surface cross-linked micelles fabricated from amphiphilic brush copolymers. 1536 Feb 82

Poly(ethylene glycol)-poly(epsilon-caprolactone) diblock copolymers PEG-PCL were synthesized by ring-opening polymerization of epsilon-caprolactone using monomethoxy poly(ethylene glycol) as the macroinitiator and calcium ammoniate as the catalyst. Obvious mutual influence between PEG and PCL crystallization was studied by altering the relative block length. Fixing the length of the PEG block (Mn = 5000) and increasing the length of the PCL block, the crystallization temperature of the PCL block rose gradually from 1 to about 35 degrees C while that of the PEG block dropped from 36 to -6.6 degrees C. Meanwhile, the melting temperature of the PCL block went up from 30 to 60 degrees C, while that of the PEG block declined from 60 to 41 degrees C. If the PCL block was longer than the PEG block, the former would crystallize first when cooling from a molten state and led to obviously imperfect crystallization of PEG and vice versa. And they both crystallized at the same temperature, if their weight fractions were equal. We found that the PEG block could still crystallize at -6.6 degrees C even when its weight fraction is only 14%. A unique morphology of concentric spherulites was observed for PEG5000-PCL5000. According to their morphology and real-time growth rates, it is concluded that the central and outer sections in the concentric spherulites were PCL and PEG, respectively, and during the formation of the concentric spherulite, the PEG crystallized quickly from the free space of the PCL crystal at the earlier stage, followed by outgrowing from the PCL spherulites in the direction of right angles to the circle boundaries until the entire area was occupied.
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PMID:Study of the synthesis, crystallization, and morphology of poly(ethylene glycol)-poly(epsilon-caprolactone) diblock copolymers. 1536 Mar 22

The aim of present work was to investigate the influence of plasticizer on the release of theophylline from microporous-controlled tablets. Three plasticizers, acetyltributyl citrate (ATBC), castor oil, and triacetin, were included in this study. These plasticizers reduced the crystallinity of poly(epsilon-caprolactone) (PCL)/poly(ethylene glycol) (PEG)-blended films, and the most prominent change of enthalpy of fusion was the film plasticized by triacetin. This might be due to triacetin penetrating into both PCL and PEG domains. However, the lipophilic property of castor oil only allowed it to alter the crystallization of hydrophobic PCL domain. The Young's modulus and the tensile strength of films showed a decreased tendency while increasing the amount of plasticizer. The change of elongation of plasticized blended films was irregular and was dependent of the type of plasticizer. The size of micropores formed in the presence of plasticizer was larger than those micropores formed in its absence. The fatty plasticizer, castor oil, altered the thermal and mechanical performance and pore size of films via soluble in PCL domain, which resulted in the release of theophylline from castor oil plasticized-coated tablets, which in turn enhanced and closed to a constant release pattern.
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PMID:The influence of plasticizers on the release of theophylline from microporous-controlled tablets. 1545 99

In this work, the biodegradable poly(epsilon-caprolactone) (PCL)/poly(ethylene glycol) (PEG) microcapsules were prepared in the presence of SiO(2) and fragrant oil using emulsion solvent evaporation method. And SiO(2) was chemically treated in 30 wt.% hydrochloric acid and sodium hydroxide. The effect of chemical treatment on SiO(2) surfaces was studied in terms of pH, acid-base value, and N(2)/77 K gas adsorption. Image analyzer and scanning electron microscope (SEM) were used to observe the shape and surface change of the prepared microcapsules. And the variation of surface free energy of microcapsules was characterized by contact angles. The results showed that the average diameter, surface free energy, and fragrant oil release rate of microcapsules were increased with increasing the PEG ratio. Also, it was found that in the case of basic treated SiO(2), the fragrant oil adsorption capacity and release rate were decreased due to the decrease of specific surface area or the increase of acid-base interactions between basic SiO(2) and acidic fragrant oil.
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PMID:Effect of acid-base interaction between silica and fragrant oil in the PCL/PEG microcapsules. 1546 2

The purpose of this study is to investigate the microspheres (MS) based on (AB)(n) type amphiphilic multiblock copolymers for sustained and complete release of a model protein, bovine serum albumin (BSA). The MS were prepared by a modified water-in-oil-in-water (W/O/W) double emulsion method using amphiphilic multiblock copolymers consisting of poly(ethylene glycol) (PEG) and a poly(alpha-ester), poly(epsilon-caprolactone) (PCL) or poly(l-lactic acid) (PLLA). The size of MS and encapsulation efficiency of BSA within MS were not noticeably influenced by the copolymer composition used in this experiment. While BSA was completely released from PEG/PLLA MS through matrix erosion and the diffusion of BSA, it was released only to an extent of 60% from PEG/PCL MS solely through the diffusion process. However, the release of BSA from PEG/PCL MS dramatically increased and then reached 100% release in 10 days after thermal treatment of the MS at 50 degrees C for 30 min in the middle of release test (on day 15).
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PMID:Albumin loaded microsphere of amphiphilic poly(ethylene glycol)/ poly(alpha-ester) multiblock copolymer. 1548 25

To explore the application of PCL for the engineering of soft tissues, the PCL surface was first embedded in an amphiphilic moiety and then grafted with RGD peptide to enhance the growth rate of human endothelial cells (HUVEC) on the surface. To graft cell-adhesive peptide RGD on the PCL surface, the PCL surface was first etched by the selected solvent with only nanometer-scale of surface disturbance, and simultaneously embedded with DSPE-PEG [di-stearoyl-phosphatidyl-ethanolamine-methoxy-poly (ethylene glycol)] moiety. Then the PCL-PEG surface was photochemically grafted by GRGD to form PCL-PEG-RGD surface. PCL and the modified surfaces were characterized by surface morphology, surface disturbance, contact angles, ATR-FTIR functional group analysis, and the growth rate of HUVEC. The surface disturbances of PCL and the modified surfaces were examined by atomic force microscope (AFM) and presented by the topography and a roughness parameter, Ra. The Ra values were 16.4 +/- 3.0, 34.8 +/- 1.6, and 12.8 +/- 0.3 nm (n = 3) for PCL, PCL-PEG, and PCL-PEG-RGD surfaces, respectively. The topographies of the surfaces and Ra values indicated that the PCL modified technique developed by this study resulted in only nanometer scale of surface disturbance. In addition to reducing surface disturbances, reducing contact angle from 73.7 degrees +/- 0.4 (n = 3) for the PCL surface to 56.9 degrees +/- 4.0 (n = 3) for the PCL-PEG surface, and the ATR-FTIR transmission spectra at 1660 cm(-1) for shoulder of amine I of PCL-PEG-RGD surface both confirmed the successful modification of PCL surfaces. HUVECs adhered well and grew on the PCL-PEG-RGD surface after 36 h incubation, whereas other surfaces did not support growth. Moreover, the viability for the relative growth rate of HUVECs on the PCL-PEG-RGD surface analyzed by MTT assay showed 8.5 times greater growth than that of the unmodified one. In conclusion, a PCL-PEG-RGD surface for enhancing the growth rate of HUVECs has been prepared by a new technique that caused only a nanometer-scale of surface disturbance. This technique and the PCL-PEG-RGD surface could be further applied to engineer soft tissues.
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PMID:Enhancing growth human endothelial cells on Arg-Gly-Asp (RGD) embedded poly (epsilon-caprolactone) (PCL) surface with nanometer scale of surface disturbance. 1557 47

The chemical preparation of structurally well-defined biodegradable amphiphilic block copolymers is now of great interest for biomedical applications and the fundamental mimetic study of biomacromolecule self-assembly. For this purpose, in this study, (R,R)-N,N'-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamine 2 as a ligand was first synthesized from 1,2-cyclohexanediamine (DACH) and was allowed to further react with AlMe3, leading to a precursor compound 3. Then, the novel five-coordinated aluminum metal complexes 4-6 and 7-8 were prepared with good yields of 80-90%, bearing various molar mass monofunctional methoxy-poly(ethylene glycol) MPEG and difunctional poly(ethylene glycol) PEG as the alkoxy moieties, respectively. By means of nuclear magnetic resonance spectrometry (NMR), mass spectrometry (MALDI-FTMS) and Fourier Transform infrared spectrometry (FT-IR), new metal aluminum complexes 4-8 were characterized as having distinct chemical structures. Utilizing the synthesized metal complexes 4-8 as novel coordination polymerization catalytic templates, biodegradable amphiphilic MPEG-b-PCL, MPEG-b-PVL, PCL-b-PEG-b-PCL and PVL-b-PEG-b-PVL were synthesized with good control of the molecular weight distribution via the ring opening polymerization of epsilon-caprolactone and delta-valerolactone monomers at 100 degrees C in toluene. In addition, the chemical and crystalline structures and the thermal properties of these block biodegradable copolymers were analyzed by means of NMR, gel permeation chromatography (GPC), wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). It was found that the melting points and crystallinities of the block copolymers synthesized strongly depended on the molecular structures of the polyether and polyester building blocks. Only one glass transition stage was detected, indicating good chain/segmental miscibility between the hydrophilic MPEG/PEG and hydrophobic PCL/PVL blocks in the non-crystalline regions. Moreover, TGA analysis exhibited typical two-step decomposition profiles with the weight-loss percentages in good agreement with block compositions from NMR calculations.
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PMID:A novel approach to biodegradable block copolymers of epsilon-caprolactone and delta-valerolactone catalyzed by new aluminum metal complexes. 1558 86

Nonviral vectors should undergo "virus-like" changes compatible with the steps of gene delivery. Poly(ethylene) glycol (PEG) shielding of DNA/polycation polyplexes protects from nonspecific interactions with the extracellular environment. pH-triggered removal of the shield within the endosome may be advantageous. Polycation and PEG were linked via acylhydrazides or pyridylhydrazines. The pyridylhydrazone prepared from polylysine and propionaldehyde-PEG showed the greatest acid-dependent hydrolysis; at pH 5, 37 degrees C for 10 min, 90% hydrolyzed, while at pH 7.4 the half-life was 1.5 h. Particle size and zeta potential measurements of the polyplexes showed complete deshielding within 1 h at pH 5, while at pH 7.4 the shield remained at 4 h, 37 degrees C. For gene transfection a targeting conjugate was also included in the polyplex, transferrin as ligand for K562 and Neuro2A cells and epidermal growth factor for HUH-7 and Renca-EGFR cells. Marker gene expression showed that the reversibly shielded polyplexes exhibited up to 2 log orders of magnitude higher gene expression in vitro and 1 log magnitude higher gene expression in an in vivo mouse model, compared to the stably shielded control polyplexes. Engineering of polyplexes with more dynamic domains is an encouraging new direction in nonviral vector design.
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PMID:Toward synthetic viruses: endosomal pH-triggered deshielding of targeted polyplexes greatly enhances gene transfer in vitro and in vivo. 1572 38

The aqueous solution of poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymers (> 15. wt. %) undergoing "clear sol-gel-turbid sol" transition as the temperature increases from 20 to 60 degrees C has been developed. Light scattering and 13C NMR study suggested that the transition mechanisms are the micellar aggregation for the clear sol to gel transition (lower transition), whereas the increase in PCL molecular motion for gel to turbid sol transition (upper transition). In contrast to the previous thermogelling biodegradable polymers with a sticky paste morphology, the powder form of the PEG-PCL-PEG triblock copolymers makes it easy to handle and allows fast dissolution in water. Therefore, the lyophilization into a powder form followed by facile reconstitution was possible. This system is believed to be promising for drug delivery, cell therapy, and tissue engineering.
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PMID:Caprolactonic poloxamer analog: PEG-PCL-PEG. 1576 55


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