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PEG Chains (peg + chain)
Selected AbstractsCationic Polyrotaxanes Effectively Inhibit Uptake via Carnitine/Organic Cationic Transporters without CytotoxicityMACROMOLECULAR BIOSCIENCE, Issue 7 2008Hideto Utsunomiya Abstract We examined the inhibitory effect of cationic polyrotaxanes, which consist of , -cyclodextrins threaded on a poly(ethylene glycol) (PEG) chain, on the activity of the intestinal carnitine/organic cation transporter, OCTN2, in OCTN2 gene-transfected HEK293/PDZK1 cells. The cationic polyrotaxanes effectively inhibited the OCTN2-mediated carnitine transport. Polyrotaxanes with a longer PEG chain exhibited a greater inhibitory effect, possibly owing to multivalent interactions with binding sites on OCTN2. These cationic polyrotaxanes were far less cytotoxic than conventional polycations, and are therefore interesting candidates as low-toxicity inhibitors of cation transport at cell surfaces. [source] Proteolytically Degradable Photo-Polymerized Hydrogels Made From PEG,Fibrinogen Adducts,ADVANCED ENGINEERING MATERIALS, Issue 6 2010Daniel Dikovsky Abstract We develop a biomaterial based on protein,polymer conjugates where poly(ethylene glycol) (PEG) polymer chains are covalently linked to multiple thiols on denatured fibrinogen. We hypothesize that conjugation of large diacrylate-functionalized linear PEG chains to fibrinogen could govern the molecular architecture of the polymer network via a unique protein,polymer interaction. The hypothesis is explored using carefully designed shear rheometry and swelling experiments of the hydrogels and their precursor PEG/fibrinogen conjugate solutions. The physical properties of non-cross-linked and UV cross-linked PEGylated fibrinogen having PEG molecular weights ranging from 10 to 20,kDa are specifically investigated. Attaching multiple hydrophilic, functionalized PEG chains to the denatured fibrinogen solubilizes the denatured protein and enables a rapid free-radical polymerization cross-linking reaction in the hydrogel precursor solution. As expected, the conjugated protein-polymer macromolecular complexes act to mediate the interactions between radicals and unsaturated bonds during the free-radical polymerization reaction, when compared to control PEG hydrogels. Accordingly, the cross-linking kinetics and stiffness of the cross-linked hydrogel are highly influenced by the protein,polymer conjugate architecture and molecular entanglements arising from hydrophobic/hydrophilic interactions and steric hindrances. The proteolytic degradation products of the protein,polymer conjugates proves to be were different from those of the non-conjugated denatured protein degradation products, indicating that steric hindrances may alter the proteolytic susceptibility of the PEG,protein adduct. A more complete understanding of the molecular complexities associated with this type of protein-polymer conjugation can help to identify the full potential of a biomaterial that combines the advantages of synthetic polymers and bioactive proteins. [source] Comparison of two approaches to grafting hydrophilic polymer chains onto polysulfone filmsJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2007Meng Tian Abstract To reduce the surface protein adsorption of polysulfone (PSf) film, we improved the hydrophilicity of this film by photochemical grafting of methoxypoly (ethylene glycol) (MPEG) derivatives on its surface. Grafting was achieved with both the simultaneous method and the sequential method. Surface analysis of the grafted film by X-ray photoelectron spectroscopy (XPS) revealed that the PEG chains had successfully grafted onto the surface of the film. The grafting efficiencies by simultaneous and sequential methods were 20.8% and 10.2%, respectively. With an atomic force microscope (AFM), the surface topography of PEG-grafted films by these two methods was compared. Static water contact angle measurement indicated that the surface hydrophilicity of the film had been improved. Protein adsorption measurement showed that the surface protein adsorption of the modified film was significantly reduced compared with that of the unmodified PSf film. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3818,3826, 2007 [source] Crystallization and morphology of cholesterol end-capped poly(ethylene glycol)JOURNAL OF APPLIED POLYMER SCIENCE, Issue 4 2007Yuan-Jin Qiu Abstract Crystallization and morphology of polyethylene glycol with molecular weight Mn = 2000 (PEG2000) capped with cholesterol at one end (CS-PEG2000) and at both ends (CS-PEG2000-CS) were investigated. It is found that the bulky cholesteryl end group can retard crystallization rate and decrease crystallinity of PEG, especially for CS-PEG2000-CS. Isothermal crystallization kinetics shows that the Avrami exponent of CS-PEG2000 decreases as crystallization temperature (Tc). The Avrami exponent of CS-PEG2000-CS increases slightly with Tc, but it is lower than that of CS-PEG2000. Compared to the perfect spherulite morphology of PEG2000, CS-PEG2000 exhibits irregular and leaf-like spherulite morphology, while only needle-like crystals are observed in CS-PEG2000-CS. The linear growth rate of CS-PEG2000 shows a stronger dependence on Tc than PEG2000. The cholesterol end group alters not only the free energy of the folding surface, but also the temperature range of crystallization regime. The small angle X-ray scattering (SAXS) results show that lamellar structures are formed in all these three samples. By comparing the long periods obtained from SAXS with the theoretically calculated values, we find that the PEG chains are extended in PEG2000 and CS-PEG2000, but they are once-folded in CS-PEG2000-CS. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2464,2471, 2007 [source] Synthesis, characterization and in vivo activity of salmon calcitonin coconjugated with lipid and polyethylene glycolJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2009Weiqiang Cheng Abstract An irreversible lipidized salmon calcitonin (sCT) analog, Mal-sCT, was previously shown to have comparable hypocalcemic activity to sCT in vivo. This study reports on the synthesis, characterization and pharmacological activity of novel PEGylated Mal-sCT analogs. Mal-sCT, prepared by conjugating sCT via thio-ether bonds with aqueous-soluble palmitic acid derivative at Cys 1 and Cys 7, was reacted with mPEG-succinimide (mPEG-Suc, 5 kDa). The products were purified and then identified by MALDI-TOF MS and HPLC. Mal-sCT was conjugated with 1 (1PEG-Mal-sCT) or 2 (2PEG-Mal-sCT) PEG chains at Lys 11 and Lys 18, the former being the preferred site of conjugation at higher mPEG-Suc/Mal-sCT ratio. Circular dichroism analysis showed the PEGylated Mal-sCT analogs to possess a robust helical conformation, while size measurement by dynamic light scattering indicated a propensity of the peptides to self-aggregate in aqueous solutions. Both 1PEG-Mal-sCT and 2PEG-Mal-sCT were more stable in rodent intestinal fluids than sCT or Mal-sCT. However, 1PEG-Mal-sCT had comparable hypocalcemic activity to Mal-sCT when injected subcutaneously in the rat, while 2PEG-Mal-sCT was inactive. 1PEG-Mal-sCT was inactive when administered orally in the rat. This study suggested PEGylation of Mal-sCT increased the stability of the lipidized peptide to enzyme degradation, but did not enhance its hypocalcemic activity. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1438,1451, 2009 [source] A Novel Micellar PEGylated Hyperbranched Polyester as a Prospective Drug Delivery System for PaclitaxelMACROMOLECULAR BIOSCIENCE, Issue 9 2008Christina Kontoyianni Abstract A hyperbranched aliphatic polyester has been functionalized with PEG chains to afford a novel water-soluble BH40-PEG polymer which exhibits unimolecular micellar properties, and is therefore appropriate for application as a drug-delivery system. The solubility of the anticancer drug paclitaxel was enhanced by a factor of 35, 110, 230, and 355 in aqueous solutions of BH40-PEG of 10, 30, 60, and 90 mg,·,mL,1, respectively. More than 50% of the drug is released at a steady rate and release is almost complete within 10 h. The toxicity of BH40-PEG was assessed in vitro with A549 human lung carcinoma cells and found to be nontoxic for 3 h incubation up to a 1.75 mg,·,mL,1 concentration while LD50 was 3.5 mg,·,mL,1. Finally, it was efficiently internalized in cells, primarily in the absence of foetal bovine serum, while confocal microscopy revealed the preferential localization of the compound in cell nuclei. [source] Nanometer-Scaled Hollow Spherical Micelles with Hydrophilic Channels and the Controlled Release of IbuprofenMACROMOLECULAR RAPID COMMUNICATIONS, Issue 23 2008De'an Xiong Abstract PS- b -PAA spherical micelles with a liquid core and a PAA shell are prepared with the assistance of 1,2-dichloroethane. During the process of adding a mixture of PNIPAM- b -P4VP and PEG- b -P4VP, multi-layered micelles with a mixed corona that consists of both PNIPAM and PEG chains are constructed through the electrostatic interaction and hydrogen bonding between the PAA block and the P4VP block. When heating above the LCST, the PNIPAM chains collapse onto the PAA/P4VP complex layer while the PEG chains still stretch into the solution through the collapsed PNIPAM layer, which leads to the formation of hydrophilic channels around the PEG chains. The ibuprofen encapsulated in the hollow space can diffuse through the channels and its release rate can be controlled by changing the ratio of PEG chains to PNIPAM chains in the corona. [source] Ultrafiltration characteristics of pegylated proteinsBIOTECHNOLOGY & BIOENGINEERING, Issue 3 2006Jessica R. Molek Abstract There is growing clinical interest in the use of pegylated recombinant proteins with enhanced stability, half-life, and bioavailability. The objective of this study was to develop a quantitative understanding of the ultrafiltration characteristics of a series of pegylated proteins with different degrees of pegylation. Sieving data were compared with available theoretical models and with corresponding results for the partition coefficient in size exclusion chromatography (SEC). The sieving coefficients of the pegylated proteins depended not only on the protein size and the total molecular weight of the polyethylene glycol (PEG) but also on the number of PEG chains. This is in sharp contrast to the partition coefficient in SEC, which was uniquely determined by the total molecular weight of the PEG and protein. This difference is due to the deformation and/or elongation of the PEG chains caused by the convective flow into the membrane pores, an effect that is not present in SEC. These results provide important insights into the transport and separation characteristics of pegylated proteins. © 2006 Wiley Periodicals, Inc. [source] Multifunctional siRNA delivery system: Polyelectrolyte complex micelles of six-arm PEG conjugate of siRNA and cell penetrating peptide with crosslinked fusogenic peptideBIOTECHNOLOGY PROGRESS, Issue 1 2010Sung Won Choi Abstract For therapeutic applications of small interfering RNA (siRNA), serum stability, enhanced cellular uptake, and facile endosome escape are key issues for designing carriers. In this study, green fluorescent protein (GFP) siRNA was conjugated to a six-arm polyethylene glycol (PEG) derivative via a reducible disulfide linkage (6PEG-siRNA). The 6PEG-siRNA conjugate was also functionalized with a cell penetrating peptide, Hph1 to enhance its cellular uptake property (6PEG-siRNA-Hph1). The 6PEG-siRNA-Hph1 conjugate was electrostatically complexed with cationic self-crosslinked fusogenic KALA peptide (cl-KALA) to form multifunctional polyelectrolyte complex micelles for gene silencing. The resultant siRNA complex formulation with multiple PEG chains showed superior physical stability and resistance to enzymatic degradation. The 6PEG-siRNA-Hph1/cl-KALA complexes exhibited enhanced GFP gene silencing efficiency for MDA-MB-435 cells in the serum containing condition. The current reducible and multifunctional polyelectrolyte complex micelles are expected to have high potential for efficient delivery of therapeutic siRNA. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] Structural Features of Interacting Complementary Liposomes Promoting Formation of Multicompartment StructuresCHEMPHYSCHEM, Issue 17 2009Zili Sideratou Dr. Abstract The structural features of complementary liposomes and factors favoring formation of multicompartment systems are investigated. Specifically, liposomal formulations consisting of PEGylated unilamellar liposomes with guanidinium moieties located at the distal end of polyethylene glycol (PEG) chains interact with complementary multilamellar liposomes bearing phosphate moieties. Furthermore, the number of PEG chains attached to the unilamellar interface of the liposomes is enhanced by incorporating PEGylated cholesterol in their bilayer. While molecular recognition of the liposomes is the driving force for initiating multicompartmentalization, it is the enhanced PEGylation at the liposomal interface that synergistically promotes fusion resulting in large and well-formed multicompartment systems. A mechanism is proposed according to which initial adhesion of the liposomes, followed by reorganization of their membrane lipids, leads to giant bilayer aggregates incorporating large liposomes. [source] Site-directed PEGylations of Thymosin , 1 Analogs and Evaluation of Their ImmunoactivityCHINESE JOURNAL OF CHEMISTRY, Issue 4 2009Jiankun QIE Abstract PEGylation is an effective way to improve the pharmacokinetic profiles of pharmaceutical proteins or peptides. But the relatively large and long PEG chains would be likely to shelter the active site of a small peptide because of its small size, compared with a protein. Therefore, the positions and numbers of PEGylation are crucial for the bioactivity of a PEGylated peptide. To elucidate the relationship between the PEGylated positions and bioactivity of a peptide drug, site-specific PEGylations were performed on Zadaxin (Thymosin , 1, T,1), which is a pharmaceutical peptide with an , -helix region, a , -turn region, and random coils. Site-specific mono-PEGylations of T,1 in different conformational regions were realized through introducing one cysteine residue into the desired positions of the peptide, followed by a coupling reaction with a thiol-attached maleimide-PEG reagent. Primary data from IFN- , production of splenocytes induced by Con A showed that the influence of PEGylation on Zadaxin was position-dependent, and mostly, positive effects were observed after PEGylation, which indicated that the position of PEGylation is important for maintaining the bioactivity of a peptide. [source] | ||||||||||||||||