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)

Polyethylene glycol (PEG)-conjugated therapeutic peptides/proteins have been shown to exhibit clinical properties superior to those of their corresponding unmodified parent molecules. However, the desirable pharmacological features gained by protein PEGylation become irrelevant if conjugates are inactivated or cannot reach their target tissues. Here we describe the design and synthesis of MAL-FMS-OSU. This bifunctional agent enables PEG chains to be linked to peptides and proteins through a slowly hydrolysable chemical bond. PEG-FMS-peptide/protein conjugates thus formed undergo spontaneous hydrolysis at a slow rate upon incubation at pH 8.5, 37 degrees C with a t(1/2) value of 8-14 +/- 2 h, generating the unmodified parent molecule. The validity of this approach was studied with exendin-4 and human growth hormone. A single subcutaneous administration of PEG(40,000)-FMS-exendin-4 facilitated a prolonged and stable reduction in glucose levels in mice (t(1/2) = 30 +/- 2 h) and exceeded the effect obtained by the same dose of the native hormone by 7-8 times.
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PMID:Prolonging the action of protein and peptide drugs by a novel approach of reversible polyethylene glycol modification. 1519 59

A series of short block length methoxy poly(ethylene glycol)-block-poly(caprolactone) diblock copolymers was synthesized and characterized in order to assess the potential of these copolymers as a micellar drug-delivery system. Varying the caprolactone:MePEG weight ratio in the reaction mixture allowed the synthesis of diblock copolymers with a MePEG molecular weight of 750 g/mol and PCL block lengths of 2, 5 or 10 repeat units. Phase diagrams of aqueous solutions of the copolymers were constructed which displayed characteristic cloud points and Krafft points. As the degree of polymerization of PCL increased, critical micelle concentration (CMC) values decreased from 6.97 x 10(-1) to 3.38 x 10(-3) g/l, partition equilibrium coefficients (Kv) increased from 1.09 x 10(4) to 22.2 x 10(4),and hydrodynamic diameters increased from 12.2 to 19.5 nm. The micelle morphology was determined to be spherical by transmission electron microscopy.
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PMID:Synthesis and micellar characterization of short block length methoxy poly(ethylene glycol)-block-poly(caprolactone) diblock copolymers. 1526 Oct 40

Diblock copolymers of poly(epsilon-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5-24.7 kDa) in the copolymer composition. Hemolytic studies showed that free DOX caused 11% hemolysis at 200 microg ml(-1), while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37 degrees C demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells.
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PMID:Micellar carriers based on block copolymers of poly(epsilon-caprolactone) and poly(ethylene glycol) for doxorubicin delivery. 1531 97

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

Biodegradable methoxy poly(ethylene glycol)/poly(-caprolactone) (MPEG/PCL) amphiphilic block copolymer nanospheres coupled to folic acid have been designed to target a folate-binding protein that is overexpressed on the surface of many tumoral cells. For this purpose, hydroxy groups terminated on the MPEG/PCL copolymer were converted into primary amino groups, which were used to conjugate with the carboxylic group of folic acid. Nanospheres were prepared by the formation of micelles of the copolymer with or without the anticancer agent paclitaxel. Folate-mediated MPEG/PCL nanospheres were compared with hydroxyl- and amino-terminated nanospheres in terms of their size, surface characteristics, and drug-loading efficiency. Regardless of the type of terminal group, the MPEG/PCL nanospheres showed a narrow size distribution with an average diameter <80 nm without paclitaxel, and an average diameter of 115 nm when loaded with the drug. The results from zeta potential and X-ray photoelectron spectroscopy measurements revealed that the folate molecules were partially exposed, and were expressed on the surface of the nanospheres allowing folate receptor recognition. In in vitro, cytotoxicity tests, the nanospheres loaded with paclitaxel showed a higher cell viability than in cases where paclitaxel was absent. Thus, folate-mediated nanospheres composed of MPEG and PCL are potentially new drug carriers for tumor cell-selective targeting treatments.
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PMID:Preparation and characterization of methoxy poly(ethylene glycol)/poly(epsilon-caprolactone) amphiphilic block copolymeric nanospheres for tumor-specific folate-mediated targeting of anticancer drugs. 1536 94

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


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