Dextran protection of erythrocytes from low‐pH‐induced hemolysis

Cudd, Amelia; Arvinte, Tudor; Schulz, Barbara; Nicolau, Claude

doi:10.1016/0014-5793(89)80741-0

Cited by 16 publications

(9 citation statements)

References 21 publications

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“…mass larger than 40kDa have been found to inhibit formation of membrane defects (pores?) induced by low pH [5]. The dextran molecules appeared to be adsorbed to the red cell membrane surface [5].…”

Section: Discussionmentioning

confidence: 97%

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Anti-human immunodeficiency virus (HIV) drug HOE/BAY 946 increases membrane hydrophobicity of human lymphocytes and specifically suppresses HIV-protein synthesis

Biesert

Adamski

Zimmer³

et al. 1990

Med Microbiol Immunol

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The polysulfated polyxylan HOE/BAY946, which has been tested in two pilot studies in ARC/AIDS patients and in asymptomatic HIV carries in Germany, was believed to act by inhibiting virus attachment to the cell. However, the drug was also found to reduce the amount of HIV particles released from infected peripheral blood mononuclear cells (PBMC) in vitro. Furthermore, preincubation of PBMC with the drug led to a partial inhibition of a following HIV infection, suggesting that the drug also affects virus entry. Electron Paramagnetic Resonance (EPR) measurements on uninfected human lymphocytes using 5-proxyl-nonane as spin label demonstrated smaller hyperfine coupling constant (aN) values in the presence of HOE/BAY946 or dextran sulfate 5000. Accordingly, h-1p/h-1H ratios were decreased, indicating increased plasma membrane hydrophobicity and a membrane-stabilizing effect of the drugs. Culture of the chronically HIV-infected monocytic cell line U937/HIV-2D194 in the presence of HOE/BAY946 specifically and drastically reduced the release of virions and the intracellular synthesis of viral proteins as determined by radioimmunoprecipitation and reverse transcriptase assays. In conclusion, although the EPR studies showed a physico-chemical effect on membrane polarity, HOE/BAY946 and dextran sulfate clearly affect processes beyond the cell membrane. Thus, in contrast to previous reports suggesting that polysulfated sugars affect HIV only by inhibiting virus binding to uninfected cells, they clearly inhibit HIV in infected cells as well and appear to have a pleiotropic mode of action. Such drugs may be less likely to result in viral resistance after prolonged application than substances acting only on one step in the life cycle of the virus.

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Section: Discussionmentioning

confidence: 97%

“…induced by low pH [5]. The dextran molecules appeared to be adsorbed to the red cell membrane surface [5]. Thus, there may be a further process relevant to the protective action of HOE/BAY 946 on the lymphocyte, namely inhibition of pore formation by increased hydrophobicity (viscosity) which is preceded by the membrane fusion process [9].…”

Section: Discussionmentioning

confidence: 99%

Anti-human immunodeficiency virus (HIV) drug HOE/BAY 946 increases membrane hydrophobicity of human lymphocytes and specifically suppresses HIV-protein synthesis

Biesert

Adamski

Zimmer³

et al. 1990

Med Microbiol Immunol

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“…Perhaps most significant, Cudd et al (1989) demonstrated that the low pH hemolysis of erythrocytes can be inhibited by dextrans of molecular weight greater than 40 000. They further demonstrated through electron microscopy that dextrans of molecular weight 150 000 form a tight association with the membrane, and this association with the membrane prevents hemolysis.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Methylcellulose and Other Polymers on Insect Cells Subjected to Laminar Shear Stress

Goldblum

Bae

Hink

et al. 1990

Biotechnology Progress

127

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The relative sensitivity of two insect cell lines to laminar shear stress was determined, and the protective effect of polymers added to the growth media of two insect cell lines, Trichoplusia ni (TN-368) and Spodoptera frugiperda (SF-9), was evaluated. TN-368 and SF-9 cells were found to be equally sensitive to laminar shear stress. Methylcellulose [0.5% (w/v) Dow E4M Methocel] and dextran [4.5% (w/v)] increased the resistance of suspended cells to lysis due to laminar shear stress by factors of up to 76 and 28, respectively, compared to cells in media without additives. It was observed that the protective effect of Pluronic F-68 was concentration-dependent: 0.2% and 0.3% (w/v) F-68 increased the resistance of SF-9 cells to shear stress by factors of 15 and 42, respectively. However, increasing the concentration to 0.5% did not significantly increase the cells' resistance compared to 0.3% (w/v). F-68 at 0.2% only increased the resistance of TN-368 cells by a factor of 6. It is believed that the protection is a result of the polymer adsorbing to the cell membrane. None of the polymer additives tested had a significant effect on SF-9 or TN-368 growth rate.

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“…The results also may be attributed to dextran molecules penetration between the carbohydrate groups on the red cell surface and that they interact with phospholipid membranes resulting in a coating of the red cell surface with dextrans. Thus, the mechanism of dextran protection may be the interaction with incipient defects, which is facilitated by the close proximity of dextrans to defect sites (Cudd et al, 1989). Transdermal delivery of 5-FU using dextran-coated CAP 7…”

Section: Hemolytic Toxicitymentioning

confidence: 99%

“…According to the results, it was found that coated nanoparticles were shown more hemocompatible than uncoated nanoparticles. The result may be due to coating with dextran on nanoparticles, as dextran also used blood plasma expender and protective effect of dextran on RBCs (Cudd et al, 1989;Jeong et al, 2006). …”

Section: Hematological Studymentioning

confidence: 99%

In-vitroandin-vivoassessment of dextran-appended cellulose acetate phthalate nanoparticles for transdermal delivery of 5-fluorouracil

Garg¹,

Rai²,

Lodhi³

et al. 2014

Drug Delivery

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The aim of this research was transdermal delivery of 5-fluorouracil (5-FU) using dextran-coated cellulose acetate phthalate (CAP) nanoparticulate formulation. CAP nanoparticles were prepared using drug-polymer ratio (1:1 to 1:3) and surfactant ratio (2.5, 5 and 10%). Dextran coating was made using aminodextran. The results showed that the optimized CAP nanoparticles (CNs) and dextran-coated CAP nanoparticles represented core-corona nanoparticles with the mean diameter of 75 ± 3 and 79 ± 2 nm, respectively, and entrapment efficiency was 82.5 ± 0.06 and 78.2 ± 0.12, respectively. Dextran-coated nanoparticles (FDCNs) and CAP nanoparticles (FCNs) showed in vitro 5-FU release upto 31 h and 8 h, respectively. Moreover, the cumulative amount of 5-FU penetrated through excised skin from FDCNs was 2.94 folds than that of the FU cream. Concentration of 5-FU in epidermis and dermis were also studied. In dermis, concentration of 5-FU was found higher in case of FDCN formulation than plain FU cream. FDCNs were found more hemocompatible in comparison to FCNs. The hematological data recommended that FDCNs formulation was less immunogenic compared to FU creams formulation. In blood level study, FDCNs exhibited 153, 12, 16.66 and 16.24-fold higher values for area under the curve, Tmax, Cmax and mean residence time (MRT) compared with those of FU cream, respectively. The in-vitro cytotoxicity was assessed using the MCF-7 by the MTT test and was compared to the plain 5-FU solution. All the detailed evidence showed that FDCNs could provide a promising tuning as a transdermal delivery system of 5-FU.

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Dextran protection of erythrocytes from low‐pH‐induced hemolysis

Cited by 16 publications

References 21 publications

Anti-human immunodeficiency virus (HIV) drug HOE/BAY 946 increases membrane hydrophobicity of human lymphocytes and specifically suppresses HIV-protein synthesis

Anti-human immunodeficiency virus (HIV) drug HOE/BAY 946 increases membrane hydrophobicity of human lymphocytes and specifically suppresses HIV-protein synthesis

Protective Effect of Methylcellulose and Other Polymers on Insect Cells Subjected to Laminar Shear Stress

In-vitroandin-vivoassessment of dextran-appended cellulose acetate phthalate nanoparticles for transdermal delivery of 5-fluorouracil

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