The Experts below are selected from a list of 207 Experts worldwide ranked by ideXlab platform
Istvan Toth - One of the best experts on this subject based on the ideXlab platform.
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A Drug Delivery Strategy: Binding Enkephalin to ASialoglycoprotein Receptor by Enzymatic
2016Co-Authors: Michelle P Christie, Waleed M Hussein, Mohamad F M Rawi, Michael P Jennings, Lauren E. Hartley-tassell, Christopher J. Day, Freda -c. E. Jen, Istvan TothAbstract:Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, aSialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation of lactose modified enkephalin in the presence of uridine-59-diphosphogalactose 4-epimerase and lipopolysaccharyl a-1,4-galactosyltransferase. Stability experiments using human plasma and Caco-2 cell homogenates showed that glycosylation considerably improved the stability of enkephalin (at least 60 % remained stable after a 2 hr incubation at 37uC). In vitro permeability experiments using Caco-2 cells revealed that the permeability of mono- and trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively, than that of enkephalin alone (Papp 3.161028 cm/s). By the methods of surface plasmon resonance and molecular modeling, we demonstrated that the enzymatic glycosylation of enkephalin enabled binding the aSialoglycoprotein receptor. The addition of a trisaccharide moiety to enkephalin improved the binding of enkephalin to the aSialoglycoprotein receptor two fold (KD = 91 mM). The docking scores from molecular modeling showed that the binding modes and affinities of the glycosylated enkephalin derivatives to the aSialoglycoprotein receptor complemente
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a drug delivery strategy binding enkephalin to aSialoglycoprotein receptor by enzymatic galactosylation
PLOS ONE, 2014Co-Authors: Michelle P Christie, Pavla Simerska, Waleed M Hussein, Mohamad F M Rawi, Lauren E Hartleytassell, Michael P Jennings, Istvan TothAbstract:Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, aSialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation of lactose modified enkephalin in the presence of uridine-5'-diphosphogalactose 4-epimerase and lipopolysaccharyl alpha-1,4-galactosyltransferase. Stability experiments using human plasma and Caco-2 cell homogenates showed that glycosylation considerably improved the stability of enkephalin (at least 60% remained stable after a 2 hr incubation at 37 degrees C). In vitro permeability experiments using Caco-2 cells revealed that the permeability of mono-and trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively, than that of enkephalin alone (Papp 3.1x10(-8) cm/s). By the methods of surface plasmon resonance and molecular modeling, we demonstrated that the enzymatic glycosylation of enkephalin enabled binding the aSialoglycoprotein receptor. The addition of a trisaccharide moiety to enkephalin improved the binding of enkephalin to the aSialoglycoprotein receptor two fold (K-D=91 mu M). The docking scores from molecular modeling showed that the binding modes and affinities of the glycosylated enkephalin derivatives to the aSialoglycoprotein receptor complemented the results from the surface plasmon resonance experiments.
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A drug delivery strategy: binding enkephalin to aSialoglycoprotein receptor by enzymatic galactosylation
PloS one, 2014Co-Authors: Michelle P Christie, Pavla Simerska, Waleed M Hussein, Mohamad F M Rawi, Michael P Jennings, Freda E.-c. Jen, Lauren E. Hartley-tassell, Christopher J. Day, Istvan TothAbstract:Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, aSialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation of lactose modified enkephalin in the presence of uridine-5′-diphosphogalactose 4-epimerase and lipopolysaccharyl α-1,4-galactosyltransferase. Stability experiments using human plasma and Caco-2 cell homogenates showed that glycosylation considerably improved the stability of enkephalin (at least 60% remained stable after a 2 hr incubation at 37°C). In vitro permeability experiments using Caco-2 cells revealed that the permeability of mono- and trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively, than that of enkephalin alone (Papp 3.1×10−8 cm/s). By the methods of surface plasmon resonance and molecular modeling, we demonstrated that the enzymatic glycosylation of enkephalin enabled binding the aSialoglycoprotein receptor. The addition of a trisaccharide moiety to enkephalin improved the binding of enkephalin to the aSialoglycoprotein receptor two fold (KD = 91 µM). The docking scores from molecular modeling showed that the binding modes and affinities of the glycosylated enkephalin derivatives to the aSialoglycoprotein receptor complemented the results from the surface plasmon resonance experiments.
Mitsuru Hashida - One of the best experts on this subject based on the ideXlab platform.
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interaction with blood components plays a crucial role in aSialoglycoprotein receptor mediated in vivo gene transfer by galactosylated lipoplex
Journal of Pharmacology and Experimental Therapeutics, 2005Co-Authors: Shintaro Fumoto, Shigeru Kawakami, Kosuke Shigeta, Yuriko Higuchi, Fumiyoshi Yamashita, Mitsuru HashidaAbstract:In this study, we evaluated the effect of blood components (whole blood and serum) on aSialoglycoprotein receptor-mediated in vivo gene transfer. The hepatic transfection activity of galactosylated lipoplex preincubated with serum was approximately 10 times higher than that without incubation after intraportal injection in mice. However, preincubation with whole blood significantly reduced hepatic transfection activity. Fluorescent resonance energy transfer analysis and agarose gel electrophoresis revealed that preincubation with serum reduced the degree of destabilization of the galactosylated lipoplex in blood, partially supporting enhanced hepatic transfection activity by preincubation with serum. Inhibition of hepatic transfection activity by predosing galactosylated bovine serum albumin indicated that the galactosylated lipoplex exposed to serum is recognized by aSialoglycoprotein-receptors on hepatocytes. Inactivation of serum prior to mixing with galactosylated lipoplex reduced liver accumulation and completely abolished enhancement of hepatic transfection activity by preincubation with active serum, suggesting that not only the stability of the lipoplex in blood but also the serum opsonin activity plays important roles. Alternatively, preincubation with inactivated serum reduced the lung accumulation and inflammatory cytokine production of galactosylated lipoplex. The information provided by this study will be valuable for the future use, design, and development of galactosylated lipoplex for in vivo aSialoglycoprotein receptor-mediated gene transfer.
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Effect of Galactose Density on ASialoglycoprotein Receptor-Mediated Uptake of Galactosylated Liposomes
Journal of pharmaceutical sciences, 2005Co-Authors: Chittima Managit, Fumiyoshi Yamashita, Shigeru Kawakami, Mitsuru HashidaAbstract:ABSTRACT: Galactosylated (Gal) liposomes containing various molar ratios of cholesten-5-yloxy- N -(4-((1-imino-2- D -thiogalactosylethyl)formamide (Gal-C4-Chol) as a ligand for aSialoglycoprotein receptors were prepared to study the effect of the galactose content of Gal-liposomes labeled with [ 3 H]cholesteryl hexadecyl ether on their targeted delivery to hepatocytes. The uptake characteristics of Gal-liposomes having Gal-C4-Chol of 1.0%, 2.5%, 3.5%, 5.0%, and 7.5% were evaluated. The uptake and internalization by HepG2 cells was enhanced by the addition of Gal-C4-Chol to the Gal-liposomes. In the presence of excess galactose, the uptake of Gal-liposomes having Gal-C4-Chol of 3.5%, 5.0%, and 7.5% was inhibited suggesting aSialoglycoprotein receptor mediated uptake. After intravenous injection, Gal-liposomes having Gal-C4-Chol of 3.5%, 5.0%, and 7.5%, rapidly disappeared from the blood and exhibited rapid liver accumulation with up to about 80% of the dose within 10 min whereas Gal-liposomes having low Gal-C4-Chol (1.0% and 2.5%) showed a slight improvement in liver accumulation compared with bare-liposomes. Gal-liposomes with high Gal-C4-Chol are preferentially taken up by hepatocytes and the highest uptake ratio by parenchymal cells (PC) and nonparenchymal cells (NPC) (PC/NPC ratio) was observed with Gal-liposomes having of 5.0% Gal-C4-Chol. We report here that the galactose density of Gal-liposomes prepared by Gal-C4-Chol is important for both effective recognition by aSialoglycoprotein receptors and cell internalization. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association
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biliary excretion of polystyrene microspheres depends on the type of receptor mediated uptake in rat liver
Biochimica et Biophysica Acta, 2001Co-Authors: Kentaro Furumoto, Ken Ichi Ogawara, Minoru Yoshida, Yoshinobu Takakura, Mitsuru Hashida, Kazutaka Higaki, Toshikiro KimuraAbstract:Hepatic uptake and biliary excretion of fluorescein isothiocyanate-labeled polystyrene microspheres with a particle size of 50 nm (MS-50) were studied in rats. Liver perfusion studies revealed that not only apo-E-mediated but also aSialoglycoprotein receptor-mediated uptake is involved in the mechanism of the serum protein-dependent uptake of MS-50 in the liver. The uptake of MS-50 mediated by apo-E contributes more to the total uptake of MS-50 by the hepatocytes than that via aSialoglycoprotein receptor in the presence of serum in the perfusate. Furthermore, it was found that MS-50 is substantially excreted into the bile by transcytosis. The extent of exocytosis of MS-50 taken up by the hepatocytes was much higher after MS-50 was endocytosed via aSialoglycoprotein receptor than after taken up via the process mediated by apo-E. On the basis of these results, a possible regulation of the intracellular sorting of ligands, depending on the receptor-mediated uptake mechanism, was inferred.
Michelle P Christie - One of the best experts on this subject based on the ideXlab platform.
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A Drug Delivery Strategy: Binding Enkephalin to ASialoglycoprotein Receptor by Enzymatic
2016Co-Authors: Michelle P Christie, Waleed M Hussein, Mohamad F M Rawi, Michael P Jennings, Lauren E. Hartley-tassell, Christopher J. Day, Freda -c. E. Jen, Istvan TothAbstract:Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, aSialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation of lactose modified enkephalin in the presence of uridine-59-diphosphogalactose 4-epimerase and lipopolysaccharyl a-1,4-galactosyltransferase. Stability experiments using human plasma and Caco-2 cell homogenates showed that glycosylation considerably improved the stability of enkephalin (at least 60 % remained stable after a 2 hr incubation at 37uC). In vitro permeability experiments using Caco-2 cells revealed that the permeability of mono- and trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively, than that of enkephalin alone (Papp 3.161028 cm/s). By the methods of surface plasmon resonance and molecular modeling, we demonstrated that the enzymatic glycosylation of enkephalin enabled binding the aSialoglycoprotein receptor. The addition of a trisaccharide moiety to enkephalin improved the binding of enkephalin to the aSialoglycoprotein receptor two fold (KD = 91 mM). The docking scores from molecular modeling showed that the binding modes and affinities of the glycosylated enkephalin derivatives to the aSialoglycoprotein receptor complemente
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a drug delivery strategy binding enkephalin to aSialoglycoprotein receptor by enzymatic galactosylation
PLOS ONE, 2014Co-Authors: Michelle P Christie, Pavla Simerska, Waleed M Hussein, Mohamad F M Rawi, Lauren E Hartleytassell, Michael P Jennings, Istvan TothAbstract:Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, aSialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation of lactose modified enkephalin in the presence of uridine-5'-diphosphogalactose 4-epimerase and lipopolysaccharyl alpha-1,4-galactosyltransferase. Stability experiments using human plasma and Caco-2 cell homogenates showed that glycosylation considerably improved the stability of enkephalin (at least 60% remained stable after a 2 hr incubation at 37 degrees C). In vitro permeability experiments using Caco-2 cells revealed that the permeability of mono-and trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively, than that of enkephalin alone (Papp 3.1x10(-8) cm/s). By the methods of surface plasmon resonance and molecular modeling, we demonstrated that the enzymatic glycosylation of enkephalin enabled binding the aSialoglycoprotein receptor. The addition of a trisaccharide moiety to enkephalin improved the binding of enkephalin to the aSialoglycoprotein receptor two fold (K-D=91 mu M). The docking scores from molecular modeling showed that the binding modes and affinities of the glycosylated enkephalin derivatives to the aSialoglycoprotein receptor complemented the results from the surface plasmon resonance experiments.
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A drug delivery strategy: binding enkephalin to aSialoglycoprotein receptor by enzymatic galactosylation
PloS one, 2014Co-Authors: Michelle P Christie, Pavla Simerska, Waleed M Hussein, Mohamad F M Rawi, Michael P Jennings, Freda E.-c. Jen, Lauren E. Hartley-tassell, Christopher J. Day, Istvan TothAbstract:Glycosylation of biopharmaceuticals can mediate cell specific delivery by targeting carbohydrate receptors. Additionally, glycosylation can improve the physico-chemical (drug-like) properties of peptide based drug candidates. The main purpose of this study was to examine if glycosylation of the peptide enkephalin could facilitate its binding to the carbohydrate receptor, aSialoglycoprotein. Firstly, we described the one-pot enzymatic galactosylation of lactose modified enkephalin in the presence of uridine-5′-diphosphogalactose 4-epimerase and lipopolysaccharyl α-1,4-galactosyltransferase. Stability experiments using human plasma and Caco-2 cell homogenates showed that glycosylation considerably improved the stability of enkephalin (at least 60% remained stable after a 2 hr incubation at 37°C). In vitro permeability experiments using Caco-2 cells revealed that the permeability of mono- and trisaccharide conjugated enkephalins was 14 and 28 times higher, respectively, than that of enkephalin alone (Papp 3.1×10−8 cm/s). By the methods of surface plasmon resonance and molecular modeling, we demonstrated that the enzymatic glycosylation of enkephalin enabled binding the aSialoglycoprotein receptor. The addition of a trisaccharide moiety to enkephalin improved the binding of enkephalin to the aSialoglycoprotein receptor two fold (KD = 91 µM). The docking scores from molecular modeling showed that the binding modes and affinities of the glycosylated enkephalin derivatives to the aSialoglycoprotein receptor complemented the results from the surface plasmon resonance experiments.
Padma V. Devarajan - One of the best experts on this subject based on the ideXlab platform.
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ASialoglycoprotein receptor targeted delivery of doxorubicin nanoparticles for hepatocellular carcinoma
Taylor & Francis Group, 2017Co-Authors: Sandhya Pranatharthiharan, Mitesh D. Patel, Vinod C. Malshe, Vaishali Pujari, Ajit Gorakshakar, Manisha Madkaikar, Kanjaksha Ghosh, Padma V. DevarajanAbstract:We report aSialoglycoprotein receptor (ASGPR)-targeted doxorubicin hydrochloride (Dox) nanoparticles (NPs) for hepatocellular carcinoma (HCC). Polyethylene sebacate (PES)-Gantrez® AN 119 Dox NPs of average size 220 nm with PDI
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evaluation of pullulan functionalized doxorubicin nanoparticles for aSialoglycoprotein receptor mediated uptake in hep g2 cell line
Cancer Nanotechnology, 2011Co-Authors: Swati A Guhagarkar, S B Majee, Abdul Samad, Padma V. DevarajanAbstract:The present study discusses evaluation of pullulan-functionalized doxorubicin nanoparticles for aSialoglycoprotein receptor-mediated uptake in the Hep G2 cell line. Doxorubicin hydrochloride (DOX) nanoparticles using polymers of different hydrophobic character, polyethylene sebacate (hydrophobic) and poly (lactic-co-glycolic acid) (intermediate hydrophobicity) with high entrapment efficiency and particle size were prepared by modified nanoprecipitation, using Gantrez AN 119 as complexing agent. Nanoparticles of Gantrez AN 119 were also prepared to represent a hydrophilic polymer. Cell uptake of DOX nanoparticles was found to be comparable to DOX solution irrespective of DOX concentration, nanoparticles size, and pullulan concentration. Furthermore, uptake of nanoparticles functionalized with or without pullulan prepared with polymers of different hydrophobic character revealed comparable uptake. Comparable uptake of DOX solution and DOX nanoparticles functionalized with or without pullulan suggest extracellular release of DOX as the mechanism of uptake from the nanoparticles. In vivo evaluation in hepatic cancer model is therefore essential to confirm the role of pullulan as aSialoglycoprotein receptors ligand.
Jiangho Geng - One of the best experts on this subject based on the ideXlab platform.
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a Sialoglycoprotein from human leukocytes functions as a ligand for p selectin
Journal of Biological Chemistry, 1994Co-Authors: Loretta Raycroft, Darwin Asa, D C Anderson, Jiangho GengAbstract:P-selectin (CD62P), a Ca(2+)-dependent lectin expressed on activated platelets and endothelial cells, functions as a receptor for myeloid and monocytoid cells. Previous reports have described a homodimeric Sialoglycoprotein from human leukocytes and HL-60 cells specifically recognized by P-selectin. We describe here a panel of monoclonal antibodies prepared against high molecular weight fractions of HL-60 cell membranes. These antibodies are of IgM isotype, bind to a approximately 240-kDa protein from human leukocyte membranes which is also reactive with P-selectin. They recognize a Ca(2+)-dependent, sialidase-sensitive determinant on myeloid and monocytoid cell lines. Each antibody specifically inhibits adhesion of neutrophils or HL-60 cells to: 1) purified P-selectin, 2) thrombin-stimulated platelets, and 3) phorbol 12-myristate 13-acetate-activated endothelial cells. These results suggest that the Sialoglycoprotein recognized by this panel of monoclonal antibodies may function as a cell surface ligand for P-selectin.
