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PubMed2001

Degradable dextran microspheres for the controlled release of liposomes.

A novel delivery concept based on the encapsulation of liposomes in biodegradable dextran microspheres was developed. The microspheres were prepared using a two-phase system, consisting of water/poly(ethylene glycol), and water/methacrylated dextran. Liposomes were encapsulated almost quantitatively and in their intact form, and were released with full preservation of their integrity. The effects of microsphere water content, degree of methacrylate substitution, and type of dextran derivative used on the release rate were investigated. The release of the liposomes from the dextran microspheres was fully controlled by the degradation rate of the spheres. This resulted, after a lag time, in a pulsed release of the liposomes from relatively rapidly degrading microspheres. On the other hand, slower degrading microspheres resulted in sustained release of liposomes over 100 days. The degradation rate of the dextran microspheres, in turn, depended on the water content, the degree of methacrylate substitution, and type of hydrolytically sensitive spacer present in the cross-links.

Dextrans↗

PubMed1991

Dextran sulfate inhibits the inositol 1,4,5-trisphosphate-induced Ca2+ release from skinned and cultured smooth muscle cells.

Dextran sulfate inhibited the inositol 1,4,5-trisphosphate (IP3)-induced decrease in 45Ca2+ content, in a dose-dependent manner, in saponin-skinned and primary cultured smooth muscle cells from the rat aorta. The maximum inhibition was observed at 3-10 mg/ml, and the IC50 was about 173 micrograms/ml. Dextran sulfate also inhibited the IP3-induced increase in 45Ca2+ efflux rate, but did not affect the caffeine-induced Ca2+ release. Dextran sulfate inhibited the specific binding of [4,5-32P]IP3 to the skinned cells, thereby indicating that it may have an effect on the IP3 receptor. Dextran (without the sulfates) had no inhibitory effect on either the IP3-induced Ca2+ release or on the specific binding of [4,5-32P]IP3. Thus, sulfate groups on the molecule of dextran sulfate may play an important role in the inhibition of the IP3-induced Ca2+ release from intracellular stores.

Animals↗

PubMed1997

Antiviral activity of derivatized dextrans on HIV-1 infection of primary macrophages and blood lymphocytes.

The present study demonstrates at the molecular level that dextran derivatives carboxymethyl dextran benzylamine (CMDB) and carboxymethyl dextran benzylamine sulfonate (CMDBS), characterized by a statistical distribution of anionic carboxylic groups, hydrophobic benzylamide units, and/or sulfonate moieties, interact with HIV-1 LAI gp120 and V3 consensus clades B domain. Only limited interaction was observed with carboxy-methyl dextran (CMD) or dextran (D) under the same conditions. CMDBS and CMDB (1 microM) strongly inhibited HIV-1 infection of primary macrophages and primary CD4+ lymphocytes by macrophage-tropic and T lymphocyte-tropic strains, respectively, while D or CMD had more limited effects on M-tropic infection of primary macrophages and exert no inhibitory effect on M- or T-tropic infection of primary lymphocytes. CMDBS and CMDB (1 microM) had limited but significant effect on oligomerized soluble recombinant gp120 binding to primary macrophages while they clearly inhibit (> 50%) such binding to primary lymphocytes. In conclusion, the inhibitory effect of CMDB and the CMDBS, is observed for HIV M- and T-tropic strain infections of primary lymphocytes and macrophages which indicates that these compounds interfere with steps of HIV replicative cycle which neither depend on the virus nor on the cell.

Amino Acid Sequence↗

PubMed1991

Direct platelet effect of low molecular weight dextran in small calibre PTFE grafts.

The thrombogenicity of synthetic vascular grafts is a major factor in occlusion of grafts when they are used to bypass small calibre arteries. In this paper, the effect of low molecular weight dextran (LMWD, Dextran-40) on graft surface-platelet interaction was studied using Indium-III-oxine labelled platelets. It was found that LMWD significantly reduced platelet deposition onto graft surfaces (P less than 0.001). Dextran had a direct antiplatelet effect independent of plasma volume expansion as dextran-soaked grafts significantly reduced platelet deposition when compared to systemic dextran administration (P less than 0.001). We therefore conclude that LMWD has a direct antiplatelet effect which is beneficial in reducing platelet deposition on synthetic PTFE grafts which may improve the early patency of such grafts.

Animals↗

PubMed1998

Covalent photolinker-mediated immobilization of an intermediate dextran layer to polymer-coated surfaces for biosensing applications.

A new method is presented for the covalent binding of dextran as an intermediate layer on surface acoustic wave (SAW) devices. For biosensing applications in aqueous media commercially available SAW devices require surface passivation to prevent corrosion of the aluminum device structures in electrolytes. Thin films of polyimide and parylene revealed exceptional passivation properties. They were used as a base for dextran immobilization. Covalent binding of dextran to polymer-coated surfaces was achieved by photoimmobilization. Aryldiazirine-functionalized bovine serum albumin served as the multifunctional light-activable linking agent (photolinker polymer). Dextran and photolinker polymer were mixed and photobonded to sensor surfaces. Essential photoimmobilization parameters were optimized. The binding of proteins to dextran applying carbodiimide chemistries was exemplified with antiurease antibodies and the feasibility of specific immunosensing was investigated on SAW sensors connected to a fluid handling system.

Acoustics↗

PubMed1998

Penetration of human vaginal and buccal mucosa by 4.4-kd and 12-kd fluorescein-isothiocyanate-labeled dextrans.

In a previous study we demonstrated that human vaginal mucosa was as permeable to water as was buccal mucosa. Water, however, is a very small molecule with a molecular weight of 18 d. To further explore similarities between these two types of mucosa with respect to permeability, it was decided to investigate the passage of two large, hydrophilic molecules across these epithelia. Specimens of fresh, clinically healthy human vaginal and buccal mucosa were taken from excised tissue obtained during vaginal hysterectomies and various oral surgical procedures. Seven biopsy materials from each specimen were mounted in flow-through diffusion cells (exposed area, 0.039 cm2), and their permeability to 4.4- and 12-kd fluorescein-isothiocyanate-labeled dextrans was determined through use of a continuous flow-through perfusion system. Dextran was detected by means of a fluorospectrophotometric method at excitation and emission wave lengths of 498 and 520 nm, respectively. Specimens were examined histologically before and after permeability experiments, and similarities between vaginal and buccal tissues were verified. No statistically significant differences between the flux values of the 4.4-kd dextran across vaginal and buccal mucosa were found. However, for the 12-kd dextran the flux rate across buccal mucosa was significantly higher than the rate across vaginal mucosa. These results demonstrate that human vaginal mucosa is for practical purposes as permeable as buccal mucosa to 4.4-kd hydrophilic molecules. This further supports the hypothesis that vaginal mucosa may be a useful model for studying the passage across buccal mucosa of chemical compounds and therapeutic agents that are less than approximately 4.4 kd in molecular mass. For a 12-kd dextran the flux rate across buccal mucosa is significantly higher than the flux rate across vaginal mucosa, and the model becomes inaccurate.

Adolescent↗

PubMedDate not supplied

Polymeric conjugates of Gd(3+)-diethylenetriaminepentaacetic acid and dextran. 1. Synthesis, characterization, and paramagnetic properties.

Macromolecular conjugates of dextran and diethylenetriaminepentaacetic acid (DTPA), aimed to complex gadolinium, were synthesized to obtain contrast agents for nuclear magnetic resonance imaging with good paramagnetic properties and long intravascular persistence. These conjugates were prepared from dextran 40 (Mn = 38 kg/mol and Mw = 43 kg/mol), which was first carboxymethylated. Then amines were introduced by reacting ethylenediamine with dextran carboxylic acid groups in the presence of 2-ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline. DTPA was then covalently linked to aminated dextran by using three different coupling procedures (DTPA bisanhydride, dicyclohexylcarbodiimide/N-hydroxysuccinimide, and isobutyl chloroformate). The different final products were compared in terms of DTPA contents, molecular masses, and sizes, and it was proved that the last synthesis step led to a small fraction of cross-linked chains as Mn was between 128 and 166 kg/mol and Mw between 332 and 371 kg/mol. In spite of this partial cross-linking which theoretically decreases the complexation capacity of the dextran-linked DTPA molecules, the Gd(3+)-complexed conjugates exhibited relaxivities at 20 MHz/mol of gadolinium-2.5 times as great as that of free GdDTPA2-.

Contrast Media↗

PubMed1985

Membrane fusion due to dehydration by polyethylene glycol, dextran, or sucrose.

To determine whether polyethylene glycol (PEG) causes growth of liposomes by affecting them directly or indirectly, vesicles composed of phosphatidylcholine were exposed to increasing concentrations of Mr 15 000-20 000 PEG or Mr 40 000 dextran either by direct mixing or across a dialysis membrane. After incubation at room temperature and dilution below at least 5% (w/w) polymer, the vesicles were monitored for fluorescence energy transfer and for absorbance at 400 nm. PEG induced the same levels of dequenching or lipid mixing and increased turbidity, regardless of whether the vesicles had been mixed directly with or dialyzed against PEG. These changes occurred within 5-15 min of polymer application. It is concluded that the increased lipid mixing and/or increased turbidity, indicating vesicle growth, resulted from an indirect effect of PEG on the vesicles--most likely dehydration. Dextran, in contrast to PEG, induced less dequenching and/or less turbidity increase when vesicles were directly mixed with, as opposed to dialyzed against, dextran. Although dextran not in contact with vesicles and with osmotic activity comparable to PEG was able to cause a degree of membrane fusion similar to that of PEG, therefore, the dehydrating effect of dextran could be mitigated if it were allowed to interact with vesicles. In further support of membrane dehydration as a precursor to membrane fusion, lipid mixing among sonicated and sonicated, frozen-thawed vesicles dialyzed against sucrose increased as a function of sucrose concentration. Vesicle morphology generally determined the maximal degree of membrane fusion inducible by the polymers.(ABSTRACT TRUNCATED AT 250 WORDS)

Desiccation↗

PubMed1979

Isoleucyl transfer ribonucleic acid synthetase. Competitive inhibition with respect to transfer ribonucleic acid by blue dextran.

The inhibitory effects of blue dextran and a small dye molecule derived from it (F3GA-OH) on the steady-state reaction catalyzed by Escherichia coli isoleucy-tRNA synthetase have been studied. Blue dextran gave uncompetitive inhibition with respect to Mg.ATP, mixed inhibition with respect to L-isoleucine, and competitive inhibition with respect to tRNA. The small dye molecule (F3GA-OH) was also competitive with respect to tRNA. These inhibition patterns were not consistent with the bi-uni-uni-bi Ping Pong mechanism generally accepted for aminoacyl-tRNA synthetases. They were consistent with a mechanism in which a second L-isoleucine is bound after isoleucyl-AMP synthesis and before transfer of the isoleucyl moiety to tRNA. Enzyme-bound L-isoleucine lowered the affinity of the enzyme for blue dextran approximately fivefold, a value comparable to the ninefold lowering of the enzyme's affinity for tRNA upon binding L-isoleucine. The affinity of the synthetase for F3GA-OH (K1 = 1.0 X 10(-7) M) is approximately fivefold higher than its affinity for blue dextran (K1 = 5.3 X 10(-7) M). These results indicate that blue dextran and its derivatives may be useful for kinetic and physical studies of polynucleotide binding sites on proteins as well as NAD and ATP sites.

Amino Acyl-tRNA Synthetases↗

PubMed2001

Modulatory factors on temperature-synchronized degradation of dextran grafted with thermoresponsive polymers and their hydrogels.

Several types of dextran grafted with poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide [dextran-g-poly(NIPAAm-co-DMAAm)] with different graft lengths and numbers were synthesized in a preciously controlled fashion, and their enzymatic degradation was examined by viscosity measurement and gel permeation chromatography as a function of temperature. Degradation of dextran-g-poly(NIPAAm-co-DMAAm)s decreased with increasing the graft length below their lower critical solution temperatures (LCSTs). Above the LCST, enzymatic degradation was independent of the graft length. A larger amount of the graft chain with increasing the graft length rather than the graft number was effective to modulate the temperature-synchronized degradation. Hydrogels were prepared by cross-linking the graft copolymers using 1,6-hexamethylenediamine. While all the hydrogels have water content of about 93-96% in a wide range of temperatures, their degradation behaviors show a significant dependence on a temperature change. Such a unique property is closely related to the structure of graft copolymers such as graft lengths. Consequently, introducing thermoresponsive grafts with longer length to dextran and its hydrogels is suggested to be an important factor for modulating enzymatic degradation of dextran in synchronization with temperature.

Biocompatible Materials↗

PubMed2006

Dextran functionalized surfaces via reductive amination: morphology, wetting, and adhesion.

Dextran surface grafting density was systematically varied via a two-step process involving SiO(2) amination by aminopropyltriethoxy silane (APTES) followed by oxidized dextran (M(w) = 110 kDa) chemisorption. Dextran oxidation kinetics with sodium metaperiodate (NaIO(4)) were quantified by (1)H NMR and pH measurements. Aldehyde group formation increased with increasing oxidation time. For 0.5 h oxidation time, dried film ellipsometric thickness was constant for solution concentrations ranging from 1 to 4 mg/mL. Dextran layers with the lowest grafting density wetted fastest and displayed the lowest contact angle (theta(APTES) > theta(1 h) > theta(2,4 h) > theta(0.5 h)). Under aqueous conditions, AFM force versus displacement measurements on 0.5 and 4.0 h surfaces exhibited a single displacement jump upon retraction. The 1.0 and 2.0 h surfaces showed two jumps consistent with two populations of chains, namely, loosely and strongly bound dextran. Overall, film morphology and wetting behavior were relatively invariant with grafting density, confirming the method's robustness for preparing biomimetic coatings with consistent properties.

Amination↗

PubMed1998

The preparation of dextran microspheres in an all-aqueous system: effect of the formulation parameters on particle characteristics.

PURPOSE: The purpose of this study was to investigate the effect of the formulation parameters on the characteristics of dextran-based microspheres, prepared in an all-aqueous system. METHODS: Dextran microspheres were formed by polymerization of methacryloyl groups attached to dextran (dexMA), emulsified in an aqueous poly(ethylene glycol) (PEG) solution. DexMA/PEG/water phase diagrams were established. RESULTS: The binodals in the phase diagrams shifted to higher concentrations of dextran and PEG with decreasing molecular weight of both polymers, and with increasing degree of MA substitution. The volume-number mean diameter of the microspheres, varied between 2.5 and 20 microns. For a given formulation, the particle size was independent of the PEG/dexMA volume ratio > 40 and increased for volume ratios < 40. Furthermore, larger particles were obtained with decreasing viscosity of the continuous phase and increasing viscosity of the discontinuous phase. CONCLUSIONS: Particle characteristics of dextran microspheres prepared in an all-aqueous system, among which the size and initial water content, can be tailored by adjusting the formulation parameters.

Dextrans↗

PubMed2001

Fusion and infection of influenza and Sendai viruses as modulated by dextran sulfate: a comparative study.

We have directly compared the effect of two types of dextran sulfate with distinct molecular weights (500 kDa and 5 kDa) on the fusion activity and infectivity of both Sendai and influenza viruses, two lipid-enveloped viruses that differ in their routes of entry into target cells. To correlate membrane merging and infectivity MDCK cells were used as targets for the viruses in both approaches. In either case pronounced inhibition of virus-cell interactions by dextran sulfate was only observed at low pH, even though Sendai virus fuses maximally at pH 7.4. Although membrane merging could not be fully abolished, the inhibitory effect was always greater when the higher molecular weight dextran sulfate was used. The presence of this residual fusion activity, that could not be reduced even with high concentrations of agent, suggests that a limited number of binding sites for dextran sulfate may exist on the viral envelopes. The compounds also inhibited fusion of bound virions, and all results could be reproduced using erythrocyte ghosts as target membranes in the fusion assay, instead of MDCK cells. In agreement with these observations only the infectivity of influenza virus (which requires a low pH-dependent step to enter target cells) was affected by dextran sulfate, again the higher molecular weight compound showing a more pronounced inhibitory effect.

Cell Membrane↗

PubMed1995

The in vitro characterization and biostability of 99mTc-dextran and its accumulation within the inflamed paws of adjuvant-induced arthritic rats.

The in vitro and in vivo stability in normal and adjuvant-induced arthritic rats of 99mTc-dextrans (10, 40 and 500 kDa) have been investigated. The circulation half-lives were molecular weight dependent, with 10 and 40 kDa fractions being cleared relatively rapidly due to their ability to cross the glomerular basement membrane. The 500 kDa dextran was eliminated more slowly although 79% had been removed from the circulation 4 h post injection which probably was due to its degradation by dextranases and subsequent glomerular excretion. Dextran accumulation by the RES was found to be similar for all molecular weight preparations with no significant differences found. The sequestration of the dextrans by tissues of the RES (liver, spleen and lung) was independent of clearance rate. No differences were seen between normal and arthritic groups. Accumulation of the polymers by inflamed paws greatly exceeded that of normal paws for the 10 kDa (5-fold) and 500 kDa (6-fold) although no differences were seen with the 40 kDa dextran.

Animals↗

PubMed1998

Effect of heparin on dextran sulfate sodium-induced colitis.

Heparin has been shown to ameliorate inflammatory bowel disease in several series. In addition to its anticoagulant properties, heparin has numerous other effects that may be beneficial in inflammatory bowel disease. Other sulfated polysaccharides, such as dextran sulfate, cause colitis in mice through unknown mechanisms. We postulate that dextran sulfate and heparin may act via similar pathways with opposite effects. To examine this thesis, the effect of heparin on dextran sulfate-induced colitis was studied. Swiss-Webster mice were given 5% dextran sulfate in their drinking water for five days to induce colitis. Heparin was given both therapeutically after the induction of colitis and prophylactically by subcutaneous injections, with saline injections given in controls. Histologic sections of colon were randomized and graded for colitis. Heparinized animals showed no significant difference in the pattern or severity of colitis when compared to control animals. It is concluded that heparin does not ameliorate the murine colitis induced by dextran sulfate in the doses given.

Animals↗

PubMed2004

Inhibition of hyaluronan degradation by dextran sulphate facilitates characterisation of hyaluronan synthesis: an in vitro and in vivo study.

The concentration and molecular weight of hyaluronan often dictates its physiological function. Consequently full characterisation of the anabolic products and turnover rates of HA could facilitate understanding of the role that HA metabolism plays in disease processes. In order to achieve this it is necessary to interrupt the dynamic balance between concurrent HA synthesis and degradation, achievable through the inhibition of the hyaluronidases, a group of enzymes which degrade HA. The sulphated polysaccharide, dextran sulphate has been demonstrated to competitively inhibit testicular hyaluronidase in a non-biological system, but its application to in vitro biological systems had yet to be developed and evaluated. This study determined the inhibitory concentrations of dextran sulphate against both testicular and Streptomyces hyaluronidase in a cell-free and breast cancer model followed by characterisation of the effect that hyaluronidase inhibition exerted on HA synthesis and degradation. The IC(100) of dextran sulphate for both hyaluronidases in a cell-free and biological system was determined to be >or=400 microg/ml. At concentrations up to 10 mg/ml the dextran sulphate did not effect breast cancer cell proliferation or morphology, while at 400 microg/ml HA degradation was totally inhibited, enabling an accurate quantitation of HA production as well as characterisation of the cell-associated and liberated HA. FACS quantitation of the HA receptor CD44, HA synthase and the hyaluronidases HYAL 1 and HYAL 2 demonstrated that dextran sulphate down-regulated CD44 and HA synthase while upregulating the hyaluronidases. These results suggest dynamic feedback signalling and complex mechanisms occur in the net deposition of HA in vivo.

Animals↗

PubMed2003

Aerosolized surfactant and dextran for experimental acute respiratory distress syndrome caused by acidified milk in rats.

BACKGROUND: Inhibition of pulmonary surfactant by plasma-derived proteins is an important pathogenetic factor of acute respiratory distress syndrome (ARDS). Inhalation of aerosolized surfactant may be suitable for early treatment of ARDS. However, requirement of a high dose is a drawback. Because dextran reverses surfactant inhibition, we examined whether dextran improves the therapeutic effects of aerosolized surfactant in rats with experimental ARDS. METHODS: Acidified milk (pH 1.8, 1.5 ml kg(-1)) was injected into the trachea of the rats ventilated with pure oxygen using 2.45 kPa peak inspiratory pressure and 0.74 kPa positive end-expiratory pressure. When PaO2 decreased to <13 kPa, the rats were assigned to four groups: control group (n = 8), receiving no material; D-only group (n = 6), receiving aerosolized dextran for 45 min; S-only group (n = 8), receiving aerosolized modified natural surfactant (MNS) for 30 min; and S-plus-D group (n = 9), receiving aerosolized MNS for 30 min followed by aerosolized dextran for 15 min. RESULTS: In the control group and D-only groups, the mean PaO2 remained at <10 kPa for 180 min. In the S-only and S-plus-D groups, the PaO2 increased to 50 kPa (P < 0.01 vs. untreated). The PaO2 of the surfactant-only group gradually decreased to <17 kPa at 180 min, whereas the PaO2 of the S-plus-D group was maintained at >38 kPa for 180 min (P < 0.01 vs. S-only group). CONCLUSION: Inhalation of aerosolized dextran potentiates the effects of aerosolized surfactant by prolonging the therapeutic response.

Aerosols↗

PubMed1991

Molecular size of retinal vascular leakage determined by FITC-dextran angiography in patients with posterior uveitis.

In order to investigate the selective breakdown of the blood-retinal barrier in posterior uveitis angiograms were performed using fluorescein-conjugated dextrans (FITC-dextrans) of different molecular weights (150-kDa, 20-kDa, and 4-kDa) in two healthy controls and six patients with posterior uveitis, and the results compared with those of conventional fluorescein angiography. The smallest FITC-dextran could not penetrate the healthy blood-retinal barrier. Leakage of FITC-dextrans of all sizes was seen from swollen optic discs; dextrans of 4-kDa and 20-kDa leaked from areas of macula oedema; and retinal new vessels allowed the passage of 4-kDa molecules only. These results indicate that there is a differential breakdown of the blood-retinal barrier according to molecular size in various clinical situations associated with posterior uveitis.

Adult↗