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  • Chemistry  (3)
  • blood brain barrier  (2)
  • multidrug resistance  (2)
  • 1995-1999  (7)
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  • 1
    ISSN: 1573-904X
    Schlagwort(e): pluronic block copolymer ; intestinal delivery ; drug ; micelles ; blood brain barrier
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. Using polarized bovine brain microvessel endothelial cells (BBMEC) monolayers as in vitro model of the blood brain barrier and Caco-2 monolayers as a model of the intestinal epithelium, the present work investigates the effects of Pluronic P85 block copolymer (P85) on the transport of the P-gycoprotein (P-gp)- dependent probe, rhodamine 123 (R123). Methods. The permeability and cell efflux studies are performed with the confluent cell monolayers using Side-Bi-Side diffusion cells. Results. At concentrations below the critical micelle concentration, P85 inhibits P-gp efflux systems of the BBMEC and Caco-2 cell monolayers resulting in an increase in the apical to basolateral permeability of R123. In contrast, at high concentrations of P85 the drug incorporates into the micelles, enters the cells and is then recycled back out to the apical side resulting in decrease in Rl 23 transport across the cell monolayers. Apical to basolateral permeability of micelle-incorporated R123 in BBMEC monolayers was increased by prior conjugation of P85 with insulin, suggesting that modified micelles undergo receptor-mediated transcytosis. Conclusions. Pluronic block copolymers can increase membrane transport and transcellular permeability in brain microvessel endothelial cells and intestinal epithelium cells. This suggests that these block copolymers may be useful in designing formulations to increase brain and oral absorption of select drugs.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    ISSN: 1573-904X
    Schlagwort(e): block copolymer ; cancer ; multidrug resistance ; Pluronic
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. Using monolayers of human pancreatic adenocarcinoma cells (Panc-1) that express multidrug resistance-associated protein (MRP), the present work investigates the effects of Pluronic block copolymers on the functional activity of MRP. Methods. The studies examined the accumulation and efflux of the MRP selective probe fluorescein (FLU) in Panc-1 cell monolayers with and without Pluronic P85 (P85), Pluronic L81 (L81) and Pluronic F108 (F108). Results. Treatment of Panc-1 cells with P85 resulted in concentration-dependent increases in FLU accumulation and elimination of FLU sequestration in vesicular compartments in these cells. The effects of P85 were selective for FLU in the Panc-1 cell monolayers. Inhibition of MRP-mediated transport was dependent on the composition of Pluronic block copolymer: the more hydrophobic copolymer had the greater effect on FLU uptake in Panc-1 monolayers (L81 〉 P85 〉 F108). Conclusions. This paper demonstrates for the first time that Pluronic block copolymers inhibit multidrug resistance-associated protein (MRP). The similarities in the effects of Pluronic block copolymers on MRP and P-glycoprotein drug efflux systems suggest that a single unifying mechanism may explain the inhibition observed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    ISSN: 1573-904X
    Schlagwort(e): doxorubicin ; rhodamine ; multidrug resistance ; Pluronic ; block copolymers ; hypersensitization
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. Previous studies have demonstrated that Pluronic block copolymers hypersensitize multiple drug resistant (MDR) cancer cells, drastically increasing the cytotoxic effects of anthracyclines and other anticancer cytotoxics in these cells. This work evaluates the dose dependent effects of these polymers on (i) doxorubicin (Dox) cytotoxicity and (ii) cellular accumulation of P-glycoprotein probe, rhodamine 123 (R123) in MDR cancer cells. Methods. Dox cytotoxicity and R123 accumulation studies are performed on monolayers of drug-sensitive (KB, MCF-7, Aux-Bl) and MDR (KBv, MCF-7/ADR, CHrC5) cells. Results. Both tests reveal strong effects of Pluronic copolymers observed at concentrations below the critical micelle concentration (CMC) and suggest that these effects are due to the copolymer single chains ('unimers'). Using block copolymers with various lengths of hydrophobic propylene oxide (PO) and hydrophilic ethylene oxide (EO) segments these studies suggest that the potency of Pluronic unimers in MDR cells increases with elevation of the hydrophobicity of their molecule. Optimization of Pluronic composition in R123 accumulation and Dox cytotoxicity studies reveals that Pluronic copolymers with intermediate lengths of PO chains and relatively short EO segments have the highest net efficacy in MDR cells. Conclusions. The relationship between the structure of Pluronic block copolymers and their biological response modifying effects in MDR cells is useful for determining formulations with maximal efficacy with respect to MDR tumors.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    New York : Wiley-Blackwell
    Biopolymers 35 (1995), S. 523-531 
    ISSN: 0006-3525
    Schlagwort(e): Chemistry ; Polymer and Materials Science
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: The reaction of competitive binding of two polyanions - DNA and synthetic fluorescence-tagged poly(methacrylate) (PMA*) - with the polycation-quencher poly(N-ethyl-4-vinyl-pyridinium) (PEVP) was studied by fluorescence quenching technique. It was found that ability of DNA to displace PMA *from the water-soluble nonstoichiometric interpolyelectrolyte complex (NPEC) formed by PMA* and PEVP - NPEC(PMA*-PEVP) - and to form water-soluble NPEC(DNA-PEVP) \documentclass{article}\pagestyle{empty}\begin{document}$$ NPEC(PMA^{*}\hbox{-}PEVP) + DNA \Leftrightarrow NPEC(DNA\hbox{-}PEVP) + PMA^{*}$$\end{document} can be determined by the parameter Ψ = PPMA*/PPEVP where PPMA* and PPEVP are the degrees of polymerization of PMA* and PEVP, respectively. In the case of Ψ 〈 1 the decrease of Ψ leads to the shift of the reaction equilibrium to the right, which can be explained by the gain of entropy due to the increase of the total number of polymeric particles in the solution. Introduction of alkali metal cations into the reaction mixture results in the shift of the reaction equilibrium, and according to their ability to shift the equilibrium to the right the cations can be arranged in the series Na+ 〉 K+ 〉 Li+. The substitution of native DNA by denatured DNA practically does not affect the reaction equilibrium in solutions of NaCl and KCl but considerably shifts it to the right in solutions of LiCl. The data obtained are in accordance with the differences in the selectivity of alkali cations binding with competitive polyanions. © 1995 John Wiley & Sons, Inc.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    ISSN: 1573-904X
    Schlagwort(e): blood brain barrier ; intestinal barrier ; MRP ; P-gp ; Pluronic block copolymer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Purpose. Previous studies demonstrated that inhibition of P glycoprotein (P-gp) by Pluronic P85 (P85) block copolymer increases apical (AP) to basolateral (BL) transport of rhodamine 123 (R123) in the polarized monolayers of bovine brain microvessel endothelial cells (BBMEC) and Caco-2 cells. The present work examines the effects of P85 on the transport of fluorescein (Flu), doxorubicin (Dox), etoposide (Et), taxol (Tax), 3′-azido-3′-deoxythymidine (AZT), valproic acid (VPA) and loperamide (Lo) using BBMEC and Caco-2 monolayers as in vitro models of the blood brain barrier and intestinal epithelium respectively. Methods. Drug permeability studies were performed on the confluent BBMEC and Caco-2 cell monolayers mounted in Side-Bi-Side diffusion cells. Results. Exposure of the cells to P85 significantly enhanced AP to BL permeability coefficients of Flu, Tax, Dox and AZT in both cell models. Further, P85 enhanced AP to BL transport of Et, VPA and Lo in Caco-2 monolayers. No changes in the permeability coefficients of the paracellular marker mannitol were observed in the presence of the copolymer. Conclusions. P85 increases AP to BL permeability in BBMEC and Caco-2 monolayers with respect to a broad panel of structurally diverse compounds, that were previously shown to be affected by P-gp and/ or multidrug resistance associated protein (MRP) efflux systems. Broad specificity of the block copolymer effects with respect to drugs and efflux systems appears to be a valuable property in view of developing pharmaceutical formulations to increase drug accumulation in selected organs and overcome both acquired and intrinsic drug resistance that limits the effectiveness of many chemotherapeutic agents.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Weinheim : Wiley-Blackwell
    Macromolecular Chemistry and Physics 199 (1998), S. 1057-1062 
    ISSN: 1022-1352
    Schlagwort(e): Chemistry ; Polymer and Materials Science
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie , Physik
    Notizen: The competitive binding of fluorescence-tagged poly(methacrylate) polyanions and poly(phosphate) polyanions with different poly(N-alkyl-4-vinylpyridinium) polycation quenchers (alkyl = methyl, ethyl and propyl) was studied in the region 278÷333 K by fluorescence quenching technique. The equilibrium of this interpolyelectrolyte substitution reaction proved to be temperature sensitive except in the case when the poly(N-methyl-4-vinylpyridinium) polycation was used. Thermodynamic parameters of the reaction were determined. The possibility of effective temperature control of the interpolyelectrolyte reaction might be important for understanding, prediction and utilization of transformation processes of complex particles formed by electrostatically complementary (biological) macromolecules.
    Zusätzliches Material: 9 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    ISSN: 0947-6539
    Schlagwort(e): liposomes ; phospholipids ; surfactants ; vesicles ; Chemistry ; General Chemistry
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: A combination of electrophoresis, dynamic light scattering, conductometry, and fluorescence spectroscopy was applied to investigate vesicles (both in the “solid” and “liquid” states) that had been imparted with electric charge through the incorporation of ionic amphiphiles. These amphiphilic compounds comprised cardiolipin (with two negative charges), sodium dodecyl sulfate (with one negative charge), and cetylpyridinium bromide (with one positive charge). By this means it was discovered that negative vesicles could be converted into neutral vesicles, and then into positive vesicles, by the addition of a cationic surfactant. The amount of cationic surfactant required for the conversion depended upon the mobility of the surfactant within the bilayer. Vesicles were found to be capable of absorbing large amounts of surfactant, both cationic and anionic, before ultimately disintegrating and releasing their contents. Mixtures of cationic and anionic vesicles were able to exchange surfactant, and thereby neutralize each other's charges, without any concurrent vesicle fusion. This phenomenon is reliable only if the vesicles are in the liquid state. Finally, a biphasic exchange process was observed in which a surfactant rapidly departs from one bilayer and then enters another, while a fluorescently labeled lipid travels the reverse path only slowly.
    Zusätzliches Material: 7 Ill.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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