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PubMed1993

Entrapment of dextran in plant cell capsules by reversible change of cell wall permeability.

Vesicular packing material (VP) made of clusters of extracted higher plant cells with the intact framework of their cell wall was used so far for permeation chromatography (vesicle chromatography). The objective of this study was to devise a method to entrap dextran in the vesicles. This can provide a means to entrap biocatalysts and secondly, to create aqueous two-phase systems with a stationary dextran phase for liquid-liquid partition chromatography. Dextran of molecular sizes above the separation limit of the plant cell wall cannot permeate into the intracellular space in aqueous medium. However, in hydrophilic organic solvent/water mixtures, dextran molecules can diffuse into the capsules. The removal of the organic solvent leaves the dextran trapped inside. There was an inverse correlation between the percentage of dextran permeating through the cell wall (Pperm) and the concentration of solvent required for dextran precipitation. The increase of permeability is therefore considered to be caused, to a great extent, by the decrease of the effective size of dextran molecules due to decreased solvation. Pperm was inversely correlated to the dielectric constants and the polarities of the solvents and, in the case of protic solvents, the hydrogen-bond acidities. No correlation was found to the hydrogen-bond basicities.

Cell Membrane Permeability↗

PubMed1994

Enhanced immunogenicity of protein-dextran conjugates: I. Rapid stimulation of enhanced antibody responses to poorly immunogenic molecules.

In view of our observation that anti-immunoglobulin antibody conjugated to high-molecular-weight dextran stimulates high levels of B-cell activation (Brunswick et al. J. Immunol. 1989, 143, 1239), we coupled T cell-dependent antigens to dextran. When mice were immunized, in the absence of adjuvant, with a BSA-dextran conjugate (BSA-dex), a persistent, high-titre anti-BSA IgG1 response was induced. Titres were dose-dependent and seen with as little as 10 micrograms of conjugated protein. Anti-BSA titres were detected as early as day 7, usually peaked at about day 14 and persisted for at least 4 weeks. Anti-hapten antibodies were also elicited in mice that were immunized with haptenated BSA covalently bound to dextran, and secondary responses could be induced even after inoculation of the unconjugated protein. Covalent attachment of the protein to the polymer was necessary, and the response was specific, as coinjection of BSA-dex and an unrelated antigen, goat IgG, did not elicit detectable anti-goat antibodies. The immunogenic potential of these conjugates did not depend on the ability of the dextran carrier to induce antibody, inasmuch as they stimulated high levels of anti-protein antibody in mice unresponsive to dextran. A minimum size dextran polymer was required for enhanced immunogenicity as conjugates of BSA with dextran of molecular mass 500 or 2000 kDa but not of 70 kDa gave detectable anti-BSA titres.

Adjuvants, Immunologic↗

PubMed1983

Advantages of dextran 70 over Ringer acetate solution in shock treatment and in prevention of adult respiratory distress syndrome. A randomized study in man after traumatic-haemorrhagic shock.

Twenty-three patients aged 20-58 years in a serious state of shock and suffering from major pelvic and femoral fractures sustained in traffic accidents were studied. As initial fluid management, either dextran 70 (1000-1500 ml) together with Ringer's acetate solution (2000-3000 ml), or Ringer's acetate alone (5000-8000 ml), was administered on a random basis. Thus, 12 patients received dextran and 11 patients crystalloid treatment to counteract shock. Both groups were given whole blood. The resuscitation time--i.e. the interval from the start of fluid therapy until a stable circulatory condition was achieved--was significantly shorter (P less than 0.001) in the dextran group (108 +/- 18 min; mean +/- S.D.) than in the Ringer group (170 +/- 43 min). During the post-resuscitative observation period of 6 days the dextran patients were given 500 ml of dextran daily, while the Ringer group did not receive any colloidal solution. To maintain a stable circulation and a urinary output above 50 ml/h the Ringer patients required significantly more (P less than 0.001) crystalloid solution (910 +/- 300 ml) daily than the dextran patients (460 +/- 400 ml). The frequency of adult respiratory distress syndrome (ARDS) was significantly lower (P less than 0.05) in the dextran group (0 of 12) than in the Ringer group (4 of 11). Thus, in the initial treatment of traumatic-haemorrhagic shock and in the post-resuscitative period dextran 70 would seem of advantage over Ringer's acetate both in shortening the shock period and in reducing the frequency of adult respiratory distress syndrome.

Adult↗

PubMed1993

The effect of the type of colloid on the efficacy of hypertonic saline colloid mixtures in hemorrhagic shock: dextran versus hydroxyethyl starch.

Colloids increase and prolong the efficacy of hypertonic saline solutions in hemorrhagic shock. We compared the efficacy of dextran 60 and hydroxyethyl starch (HES) 200,000/0.5 at iso-oncotic concentrations of 6.5 or 6% in a 7.5% NaCI solution. Thirty-two rabbits were bled to maintain a mean arterial pressure at 35 mmHg. Twenty-five percent of the shed blood volume was replaced after 40 min by bolus infusion either with hypertonic dextran (HS-DEX) (n = 16) or with hypertonic hydroxyethyl starch (HS-HES) (n = 16). The animals were then observed for a 120-min period. In both groups immediate and complete restoration of cardiovascular function was achieved in up to 30 min and adequate restoration maintained for 60 min after infusion. During the subsequent 60 min signs of insufficient oxygen supply indicated the recurrence of near shock levels. Greater stability of hemodynamic efficacy was observed when dextran was added to hypertonic saline. The decrease in mean arterial pressure was lower in the dextran group (P < 0.05). The subsequent increase in avDO2 (v. cava sup.) was approximately 50% lower with dextran (1 ml/dl compared to 1.8 ml/dl); (P < 0.05). These differences occurred primarily within the initial 15 min although the differences in mean arterial pressure were recorded only after 30-60 min. A 50% reduction in lactate levels (1.1 compared to 2.0 mmol; P < 0.05) in immediate response to reinfusion indicates an increased lactate absorption and thus improved perfusion of poorly perfused tissue in the dextran group. A further, important difference may be due to the different effects on the microcirculation. As evidenced by a decline in the end-expiratory arterial CO2 gradient, dextran effected a significant (P < 0.01) improvement in decreased pulmonary CO2 emission during shock. This indicates a greater rise of blood flow in poorly perfused, ventilated pulmonary areas. In summary, in our model dextran appeared to be the superior colloid compared to HES, particularly during the first hour after initiation of treatment, although direct proof of an improved long term outcome has not been demonstrated.

Acidosis↗

PubMed1979

Inhibition of factor VIII-associated platelet aggregation by heparin and dextran sulfate, and its mechanism.

Both ristocetin-induced aggregation in the presence of human factor VIII and bovine factor VIII-induced aggregation of washed normal human platelets were inhibited or reversed by the addition of heparin or dextran sulfate. These actions of dextran sulfate were stronger than those of heparin, and dependent on the sulfur content of dextran sulfate. In order to study the mechanism of actions of dextran sulfate and heparin, the affinity chromatographic experiment of factor VIII in human and bovine plasma, respectively, was carried out by using a dextran sulfate- and a heparin-Agarose column. Both human and bovine factor VIII have a strong affinity for dextran sulfate with high sulfur content and a weak affinity for heparin, but no affinity for dextran sulfate with low sulfur content. From these results, it is suggested that dextran sulfate or heparin binds directly the human and bovine factor VIII, which is an essential factor for the maintenance of the weak interplatelet bonds, and either inhibits or reverses the platelet aggregation.

Chromatography, Affinity↗

PubMed2006

Dextran and 5-aminosalicylic acid (5-ASA) conjugates: synthesis, characterisation and enzymic hydrolysis.

Mesalamine (5-aminosalicylic acid) is the drug of choice for the treatment of Crohn's disease. A scheme for the synthesis of 5-aminosalicylic acid (5-ASA) conjugates of dextrans was developed with a focus on Crohn's disease applications. Dextrans were oxidised using sodium periodate (NaIO(4)), where the aldehyde groups formed were coupled with the alpha-amino (-NH(2)) group of 5-ASA. The resulting imine bonds were unstable in water and were consequently reduced to secondary amine groups. The effects of different aspects of the conjugation reaction were studied. These included the following: the molecular weight of the dextrans, the molar proportion of NaIO(4) to the dextrans (for periodate oxidation), the pH of the conjugation solutions, the ratio 5-ASA to oxidised polysaccharide and the relationship between the degree of conjugation and the amount of enzyme hydrolysis. Conjugates incubated in HCl were stable in 0.5 and 1.0M HCl, but they underwent degradation in 2.0 and 4.0M HCl. Dextrans (MW 20,000) with various degrees of oxidation (12%, 26%, 46%, 65%, 90% and 93%) were also prepared. Each oxidised dextran sample was conjugated with 5-ASA, and the product was quantified by high-performance liquid chromatography (HPLC). Dextrans with a maximum degree of oxidation (93%) unsurprisingly gave maximum conjugation of 5-ASA (49.1mg per 100mg of product) but were resistant to dextranase hydrolysis. Less oxidised dextrans (12%) conjugated proportionally less 5-ASA (15.1mg per 100mg of product) but were successfully hydrolysed by dextranase, suggesting their potential applications for the treatment of Crohn's disease in the distal ileum and proximal colon.

Aminohydrolases↗

PubMed2005

Liquid chromatography of dextrans on porous silica beds.

Kinetics, equilibrium isotherms and chromatography retention times for sorption of dextrans T-10, T-20, T-40, T-70, T-110, T-161, T-250 and T-500 on porous silica were measured at 25 degrees C. The Henry constant and retention factors for the dextrans were obtained. The values of the partition coefficient for the distribution of the dextrans between the bulk solution and the pore space were calculated within the framework of a pore volume filling model with consideration given to the ratio between the sizes of the macromolecular coils and the pore inlet. The measurements showed that this parameter depends on the structure of the sorbent and the molecular mass distribution of the dextran. The interaction of aqueous dextran solution with porous silica is characterized by the sieve effect. Large macromolecular coils of dextran T-161 cannot penetrate into the pore space of the silica sorbent with pore diameter 14 nm. The difference in Henry law constants calculated from adsorption and chromatographic data for dextrans T-70 and T-110 can be explained by the slow diffusion of dextran macromolecules into silica pores under chromatographic conditions.

Adsorption↗

PubMed1999

Lowering of trichosanthin immunogenicity by site-specific coupling to dextran.

Trichosanthin is a type I ribosome-inactivating protein possessing a broad spectrum of biological and pharmacological activities. Therapeutic use of this compound is hampered by its immunogenicity. It was shown earlier that coupling of dextran to trichosanthin can increase plasma half-life and reduce antigenicity. However, the site where dextran attaches to trichosanthin cannot be controlled; ideally, it should be at or near the antigenic determinant. The present study attempted to couple dextran to trichosanthin at a potential antigenic site. By site-directed mutagenesis, two sites, R29 and K173, were replaced by cysteine, and dextran was coupled to the newly created cysteine residues. The dextran-trichosanthin complex retained 50% of abortifacient activity and had a mean residence time in rats 27-fold longer than natural trichosanthin. Acute hypersensitivity reaction in guinea pigs was reduced greatly after coupling of K173C (a trichosanthin mutant with lysine-173 replaced by cysteine) to dextran. Compared with natural trichosanthin, dextran-K173C had a decrease in IgG and IgE response, whereas the coupling of R29C (a trichosanthin mutant with arginine-29 replaced by cysteine) to dextran did not show significant reduction of immunogenicity. This suggests that K173 but not R29 is located at or near an antigenic determinant. This study has demonstrated an alternative approach for mapping of antigenic determinants. The information obtained is also useful in producing an improved trichosanthin derivative for therapeutic use.

Acute-Phase Reaction↗

PubMed1987

Affinity partitioning of enzymes using dextran-bound procion yellow HE-3G. Influence of dye-ligand density.

The dye Procion Yellow HE-3G was bound to dextran of molecular weight 70,000 and the partitioning of this dye-polymer within an aqueous two-phase system containing dextran and poly(ethylene glycol) was studied as function of ligand density, polymer concentration, type of salt, concentration of salt and concentration of dye-dextran. Even moderate dye:dextran molar ratios (5-8) make the partitioning strongly salt-dependent. The dye-dextran can be directed to either the upper or the lower phase with partition coefficients from 0.02 to 28 by using salts. The dye-dextran in the two-phase system affects the partitioning of dye-binding enzymes (lactate dehydrogenase, glucose-6-phosphate dehydrogenase, 3-phosphoglycerate kinase) towards the dye-containing phase. Measurements of competition with nucleotide binding show an increased affinity of the dye for the enzyme with increasing ligand:dextran ratio. Theoretical considerations indicate that 1-2 dextran molecules are attached per enzyme molecule when affinity partitioning is fully developed.

Chromatography, Affinity↗

PubMed1977

Prevention of postoperative thromboembolism by dextran 40, low doses of heparin, or xantinol nicotinate.

The efficacy of dextran-40 infusions or low-dose heparin or xantinol-nicotinate administration in preventing postoperative thromboembolic complications has been investigated in a prospective, controlled, randomised trial as part of an international multicentre trial. 382 patients over the age of forty years undergoing elective major general surgery were investigated; 100 had a complete protocol in the control, 94 in the heparin, 92 in the dextran, and 32 in the xantinol-nicotinate group. 31 patients died: 13 in the control group, 10 in the heparin group, 6 in the dextran group, and 2 in the xantinol-nicotinate group. In 4 controls, 6 in the heparin group, and 1 in the dextran group the cause of death was acute pulmonary embolism. 4 further controls, 1 in the heparin group, and 2 in the dextran group had emboli found at necropsy, which either contributed to the deaths or were incidental findings. The distribution of pulmonary emboli in this study did not show the difference between the control and the heparin group reported in the multicentre trial. The 125I-fibrinogen test was done in all patients. The frequency of isotopic deep-vein thrombosis was 36-0% in the controls, 12-8% in the heparin group, 21-7% in the dextran group, and 40-6% in the xantinol-nicotinate group. The difference between the controls and the heparin groups was highly significant and between the control and the dextran group, probably significant. There were significantly more side-effects in the heparin group than in the dextran group.

Administration, Oral↗

PubMed2001

Formation of dextran hydrogels by crystallization.

In this paper, a novel method is presented for the preparation of dextran hydrogels and microspheres, based on crystallization. Although dextrans are known to be well soluble in water, precipitation was observed in concentrated aqueous solutions of low molecular weight dextran (dextran 6000), whereas for solutions of dextran with higher molecular weights (dextran 40,000 and 220,000) no precipitation was observed in the time-frame studied. The kinetics of the precipitation process were studied and showed that precipitation was faster when more concentrated dextran solutions were used. Furthermore, the precipitation process was accelerated by stirring and by the presence of salts. Depending on the precipitation time, microspheres or gels were obtained. The precipitates were insoluble in water at room temperature, but readily dissolved in boiling water or DMSO. IR spectroscopy and (modulated) differential scanning calorimetry ((M)DSC) demonstrated that the precipitates were crystalline. We hypothesize that crystallization is due to association of the chains through hydrogen bonding, induced by the large polymer/water ratio in concentrated dextran 6000 solutions.

Calorimetry, Differential Scanning↗

PubMed2003

Synthesis and characterization of biodegradable polylactide-grafted dextran and its application as compatilizer.

Brush-like biodegradable polylactide-grafted dextran copolymer (PLA-g-dextran) was by a bulk polymerization reaction using a trimethylsilyl-protected (TMS) dextran as macroinitiator and stannous octoate as catalyst. After the polymerization, the TMS groups could be easily removed by immersing the copolymer in methanol for 48 h. The PLA-g-dextran copolymers were characterized by (1)H NMR, GPC and intrinsic viscosity measurements. Besides, mouse 3T3 fibroblasts were cultured on these copolymeric substrates together with pure polylactide (PLA). Although the copolymers exhibited better hydrophilicity and cell affinity compared to pure PLA because of the incorporation of glucose units and the brush-like architecture, it was found that the cells still could not migrate into the center part of scaffold made of PLA-g-dextran copolymer. In result, PLA-g-dextran copolymers themselves were not an appropriate choice for the cell scaffold material, however, it could be used as compatilizer to ameliorate the compatibility between hydrophilic dextran and hydrophobic PLA due to its amphiphilic structure, which could improve the mechanical properties of PLA/dextran blends by reducing the phase separation between PLA and dextran. Therefore, the PLA/dextran blends, which had good cell affinity and moderate mechanical strength, might be prospect cell scaffold materials.

Animals↗

PubMed1999

Effects of nitric oxide inhibition on the spread of biotinylated dextran and on extracellular space parameters in the neostriatum of the male rat.

Volume transmission in the brain is mediated by the diffusion of neurotransmitters, modulators and other neuroactive substances in the extracellular space. The effects of nitric oxide synthase inhibition on extracellular space diffusion properties were studied using two different approaches, the histological dextran method and the real-time iontophoretic tetramethylammonium method. The spread of biotinylated dextran (mol. wt 3000) in the extracellular space was measured morphometrically following microinjection into the neostriatum of male rats. Two parameters were used to describe the spread of biotinylated dextran in brain tissue, namely, total volume of spread and the mean grey value. The nonspecific nitric oxide synthase inhibitors NG-nitro-L-arginine methyl ester (10-100 mg/kg) and NG-monomethyl-L-arginine acetate (30-200 mg/kg) decreased the total volume of spread of dextran in a dose-dependent manner. 7-Nitroindazole monosodium salt (50-100 mg/kg), a specific neuronal nitric oxide synthase inhibitor, did not change the total volume of spread of dextran. Using the tetramethylammonium method, the extracellular space diffusion properties can be described by the volume fraction (alpha = extracellular space volume/total tissue volume), tortuosity lambda (lambda2 = free diffusion coefficient/apparent diffusion coefficient in tissue), and non-specific uptake kappa' [Nicholson C. and Syková E. (1998) Trends Neurosci. 21, 207-215]. Nitric oxide synthase inhibition by NG-nitro-L-arginine methyl ester (50 mg/kg) had relatively little effect on volume fraction and tortuosity, and no changes were observed after NG-monomethyl-L-arginine acetate (20 mg/kg) or 7-nitroindazole monosodium salt (100 mg/kg) treatment. A substantial increase was found only in non-specific uptake, by 13% after NG-nitro-L-arginine methyl ester and by 16% after NG-monomethyl-L-arginine acetate, which correlates with the decreased total volume of spread of dextran observed with the dextran method. NG-Nitro-L-arginine methyl ester treatment (100 mg/kg) decreased striatal blood flow and increased mean arterial blood pressure. The changes in dextran spread and non-specific uptake can be explained by an increased capillary clearance following the inhibition of endothelial nitric oxide synthase, as neuronal nitric oxide synthase inhibition had no effect. The observed changes after non-specific nitric oxide synthase inhibition may affect the extracellular space concentration of neurotransmitters and modulators, and influence volume transmission pathways in the central nervous system by increased capillary and/or cellular clearance rather than by changes in extracellular space diffusion.

Animals↗

PubMed2000

Viscosity prediction of polyethylene glycol-dextran-water solutions used in aqueous two-phase systems.

The dynamic viscosities of aqueous polyethylene glycol and dextran, and poly(ethylene glycol)-dextran-water solutions were measured at temperatures of 30, 50 and 70 degrees C. The poly(ethylene glycol) having a relative molecular mass of 8000, and dextran samples with relative molecular masses of 37 500, 494 000, and 2 000 000 were used. A one-parameter Grunberg-like equation proposed earlier by us was used for estimating the values of viscosity of poly(ethylene glycol)-dextran-water solutions. The disposable parameter a for this temperature range was calculated as 1.81 for PEG 8000-dextran 37 500-water solutions, as 2.36 for PEG 8000-dextran 494 000-water solutions, and as 2.57 for PEG 8000-dextran 2 000 000-water solutions. It was observed that the relative errors get larger as the relative molecular mass of the dextran increases but vary between 0.00 and 9.37 in absolute value. In view of the results obtained here and before, we may claim that the proposed model works constantly well at different temperatures giving comparable values for the disposable parameter a.

Dextrans↗

PubMed1998

Quantitation of dextran 70 in peritoneal dialysate from patients administered 7.5% polyglucose.

A method using gel permeation chromatography was evaluated for the quantitation of dextran 70 in dialysate samples containing polyglucose. Dialysate samples containing dextran 70 and polyglucose were pretreated using the enzyme alpha-amylase to selectively hydrolyze the alpha(1-4)-linked polyglucose, while leaving the alpha(1-6)-linked dextran 70 intact. Following sample deproteinization with trichloroacetic acid, dextran 70 was quantitated using gel permeation chromatography with refractive index detection. This method was evaluated for accuracy, precision, specificity, linearity, range, and analyte stability. Adequate method linearity with a correlation of >0.999 was established over the range of dextran 70 concentration from 1 to 0.025 mg/ml. Method precision was approximately 2% R.S.D. and accuracy (% recovery) was approximately 98-100% in the typical sample concentration range (1-0.5 mg/ml). This method was applied to the determination of intraperitoneal fluid kinetics in continuous ambulatory peritoneal dialysis (CAPD) patients administered daily night-time intraperitoneal exchanges with either 7.5% polyglucose or 4.25% dextrose. Dextran 70 was added to the dialysis solutions to yield an initial concentration of 1 mg/ml. Dialysate samples were collected at various times over a 10-h dwell-time and assayed for dextran 70. Intraperitoneal volume profiles based on dextran 70 concentrations and drain volumes were then calculated for each dialysis solution.

Chromatography, Gel↗

PubMed1983

Hemodynamic and regional blood flow distribution responses to dextran, hydralazine, isoproterenol and amrinone during experimental cardiac tamponade.

Four different interventions were examined in dogs with cardiac tamponade. Infusion of 216 to 288 ml saline solution into the pericardium reduced cardiac output from 3.5 +/- 0.3 to 1.7 +/- 0.2 liters/min as systemic vascular resistance increased from 4,110 +/- 281 to 6,370 +/- 424 dynes . s . cm-5. Left ventricular epicardial and endocardial blood flows were 178 +/- 13 and 220 +/- 12 ml/min per 100 g, respectively, and decreased to 72 +/- 14 and 78 +/- 11 ml/min per 100 g with tamponade. Reductions of 25 to 65% occurred in visceral and brain blood flows and in a composite brain sample. Cardiac output during tamponade was significantly increased by isoproterenol, 0.5 microgram/kg per min intravenously; hydralazine, 40 mg intravenously; dextran infusion or combined hydralazine and dextran, but not by amrinone. Total systemic vascular resistance was reduced by all interventions. Left ventricular epicardial flow was increased by isoproterenol, hydralazine and the hydralazine-dextran combination. Endocardial flow was increased by amrinone and the combination of hydralazine and dextran. Right ventricular myocardial blood flow increased with all interventions except dextran. Kidney cortical and composite brain blood flows were increased by both dextran alone and by the hydralazine-dextran combinations. Blood flow to small intestine was increased by all interventions as was that to large intestine by all except amrinone and hydralazine. Liver blood flow response was variable. The most pronounced hemodynamic and tissue perfusion improvements during cardiac tamponade were effected by combined vasodilation-blood volume expansion with a hydralazine-dextran combination. Isoproterenol had as dramatic an effect but it was short-lived. Amrinone was the least effective intervention.

Aminopyridines↗

PubMed1998

Effects of heparin, desmopressin, and isovolemic hemodilution with dextran on thrombus formation in synthetic vessel grafts inserted into the vena cava of the rabbit.

The objective of this study was to investigate the effects of isovolemic hemodilution with dextran-70 on thrombus formation and blood flow in synthetic venous vessel grafts. Polytetrafluoroethylene grafts (length, 11 mm; inner diameter, 3 mm) were inserted into the vena cava of rabbits. Six groups were studied: (1) the control group; (2) animals that underwent isovolemic hemodilution with dextran-70 to a hematocrit of about 30%; (3) animals that underwent isovolemic dextran hemodilution combined with a bolus injection of heparin; (4) animals that underwent heparin treatment only; (5) animals that underwent isovolemic dextran hemodilution combined with infusion of desmopressin; and (6) animals that underwent an identical treatment to group 3 but with a 2-week, instead of a 2-day, follow-up. Vena cava blood flow was measured before and after hemodilution and graft insertion and at the termination of the experiments at 2 days (groups 1 to 5) and 2 weeks (group 6) after surgery. Graft patency and thrombus mass weight were evaluated. In the control group, most of the vessels occluded within 2 days. Hemodilution with dextran improved blood flow and reduced thrombus mass weight significantly. Desmopressin, which increases factor VIII, did not influence the effects of hemodilution with dextran, which suggests that the effects of dextran are not mediated by a reduction in the level of this coagulation factor. A single bolus dose of heparin did not reduce thrombus formation in the grafts but did potentiate the effects of isovolemic hemodilution on thrombus mass and graft blood flow. We conclude that isovolemic dextran hemodilution combined with a single bolus of heparin had beneficial long-lasting effects. The grafts in groups 3 and 6 were all patent.

Animals↗

PubMed2004

Dextran-spermine polycation: an efficient nonviral vector for in vitro and in vivo gene transfection.

Dextran-spermine cationic polysaccharide was prepared by means of reductive amination between oxidized dextran and the natural oligoamine spermine. The formed Schiff-base imine-based conjugate was reduced with borohydride to obtain the stable amine-based conjugate. The transfection efficiency of the synthetic dextran-spermine was assessed in vitro on HEK293 and NIH3T3 cell lines and found to be as high as the DOTAP/Chol 1/1 lipid-based transfection reagent. Modification of the dextran-spermine polycation with polyethylene glycol resulted in high transfection yield in serum-rich medium. Intramuscular injection in mice of dextran-spermine-pSV-LacZ complex induced high local gene expression compared to low expression of the naked DNA. Intravenous injection of a dispersion of the dextran-spermine-pSV-LacZ complex resulted with no expression in all examined organs. When the partially PEGylated dextran-spermine-pSV-LacZ complex was intravenously applied, a high gene expression was detected mainly in the liver. Preliminary targeting studies indicated that the PEGylated dextran-spermine-pSV-LacZ complex bound to galactose receptor of liver parenchymal cells rather than the mannose receptor of liver nonparenchymal cells. This work offers a new biodegradable polycation based on natural components, which is capable of transfecting cells and tissues in vitro and in vivo.

3T3 Cells↗