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Construction by molecular dynamics modeling and simulations of the porous structures formed by dextran polymer chains attached on the surface of the pores of a base matrix: characterization of porous structures.

Significant increases in the separation of bioactive molecules by using ion-exchange chromatography are realized by utilizing porous adsorbent particles in which the affinity group/ligand is linked to the base matrix of the porous particle via a polymeric extender. To study and understand the behavior of such systems, the M3B model is modified and used in molecular dynamics (MD) simulation studies to construct porous dextran layers on the surface of a base matrix, where the dextran polymer chains and the surface are covered by water. Two different porous polymer layers having 25 and 40 monomers per main polymer chain of dextran, respectively, are constructed, and their three-dimensional (3D) porous structures are characterized with respect to porosity, pore size distribution, and number of conducting pathways along the direction of net transport. It is found that the more desirable practical implications with respect to structural properties exhibited by the porous polymer layer having 40 monomers per main polymer chain, are mainly due to the higher flexibility of the polymer chains of this system, especially in the upper region of the porous structure. The characterization and analysis of the porous structures have suggested a useful definition for the physical meaning and implications of the pore connectivity of a real porous medium that is significantly different than the artificial physical meaning associated with the pore connectivity parameter employed in pore network models and whose physical limitations are discussed; furthermore, the methodology developed for the characterization of the three-dimensional structures of real porous media could be used to analyze the experimental data obtained from high-resolution noninvasive three-dimensional methods like high-resolution optical microscopy. The MD modeling and simulations methodology presented here could be used, considering that the type and size of affinity group/ligand as well as the size of the biomolecule to be adsorbed onto the affinity group/ligand are known, to construct different porous dextran layers by varying the length of the polymeric chain of dextran, the number of attachment points to the base matrix, the degree of side branching, and the number of main polymeric chains immobilized per unit surface area of base matrix. After the characterization of the porous structures of the different porous dextran layers is performed, then only a few promising structures would be selected for studying the immobilization of adsorption sites on the pore surfaces and the subsequent adsorption of the bioactive molecules onto the immobilized affinity groups/ligands.

Adsorption↗

Confocal laser scanning microscopic visualization of the transport of dextrans after nasal administration to rats: effects of absorption enhancers.

PURPOSE: To visualize the transport pathway(s) of high molecular weight model compounds across rat nasal epithelium in vivo using confocal laser scanning microscopy. Furthermore, the influence of nasal absorption enhancers (randomly methylated beta-cyclodextrin and sodium taurodihydrofusidate) on this transport was studied. METHODS: Fluorescein isothiocyanate (FITC)-labelled dextrans with a molecular weight of 3,000 or 10,000 Da were administered intranasally to rats. Fifteen minutes after administration the tissue was fixed with Bouin. The nasal septum was surgically removed and stained with Evans Blue protein stain or DiIC18(5) lipid stain prior to visualization with the confocal laser scanning microscope. RESULTS: Transport of FITC-dextran 3,000 across nasal epithelium occurred via the paracellular pathway. Endocytosis of FITC-dextran 3,000 was also shown. In the presence of randomly methylated beta-cyclodextrin 2% (w/v) similar transport pathways for FITC-dextran 3,000 were observed. With sodium taurodihydrofusidate 1% (w/v) the transport route was also paracellular with endocytosis, but cells were swollen and mucus was extruded into the nasal cavity. For FITC-dextran 10,000 hardly any transport was observed without enhancer, or after co-administration with randomly methylated beta-cyclodextrin 2% (w/v). Co-administration with sodium taurodihydrofusidate 1% (w/v) resulted in paracellular transport of FITC-dextran 10,000, but morphological changes, i.e. swelling of cells and mucus extrusion, were observed. CONCLUSIONS: Confocal laser scanning microscopy is a suitable approach to visualize the transport pathways of high molecular weight hydrophilic compounds across nasal epithelium, and to study the effects of absorption enhancers on drug transport and cell morphology.

Absorption↗

The peritoneal transport of serum proteins and neutral dextran in CAPD patients.

The peritoneal transport of five serum proteins and intravenously-administered neutral dextran was studied in 13 CAPD patients. In all patients a study was done three hours after the administration of dextran. In nine the study was repeated after 14 hours, and in six also after 38 hours. Using gel permeation chromatography of serum and dialysate it was possible to calculate fractional (relative to inulin) clearances for dextran fractions with Einstein-Stokes radii ranging from 30 to 90 A. In contrast to glomerular transport, we found that peritoneal clearances of serum proteins and corresponding dextran fractions were of a similar magnitude up to a radius of 90 A, especially in the follow-up studies. No evidence was found for a charge-selective barrier function of the peritoneum. It appeared likely that the peritoneal interstitium is probably a third compartment between blood and dialysate in which equilibrium with blood and dialysate is present for serum proteins, but initially not for dextran. For dextran this equilibrium is probably approached 14 to 38 hours after administration. The linear relationship between the reciprocal of fractional clearances and Einstein-Stokes radii indicates that restricted diffusion is the main transport mechanism of macromolecules across the peritoneal membrane. The slopes of the linear regression between the reciprocal of fractional clearances and radii ranged from 0.32 to 6.95 (slope for free diffusion 0.07) and provided an index of the permeability characteristics of the peritoneal membrane.

Adult↗

Enhanced suppression of tumor growth using a combination of NK4 plasmid DNA-PEG engrafted cationized dextran complex and ultrasound irradiation.

This investigation aims to determine experimentally whether or not ultrasound (US) irradiation is effective in enhancing the in vivo gene expression of NK4 plasmid DNA and suppressing tumor growth. NK4, composed of the NH2-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts as an HGF-antagonist and angiogenesis inhibitor. Dextran was cationized by introducing spermine to the hydroxyl groups to allow for polyionic complexation with NK4 plasmid DNA. The cationized dextran was additionally modified with poly(ethylene glycol) (PEG) molecules giving PEG engrafted cationized dextran. Significant suppression of tumor growth was observed when PEG engrafted cationized dextran-NK4 plasmid DNA complexes were intravenously injected into mice carrying a subcutaneous Lewis lung carcinoma tumor mass with subsequent US irradiation when compared with the cationized dextran-NK4 plasmid DNA complex and naked NK4 plasmid DNA with or without US irradiation. We conclude that complexation with PEG-engrafted cationized dextran in combination with US irradiation is a promising way to target the NK4 plasmid DNA to the tumor for gene expression.

Animals↗

Optimization of dextran production by Leuconostoc mesenteroides NRRL B-512 using cheap and local sources of carbohydrate and nitrogen.

Using pure components for the fermentation medium in dextran production imposes high costs on the industry. In the present study, the economic production of dextran using local and cheap sources of carbohydrate and nitrogen was investigated. Different concentrations of molasses and wheat-bran extract, after filtration, steam sterilization and pH adjustment, were inoculated with a fresh suspension of Leuconostoc mesenteroides. Cultures were incubated, and then diluted with an equal volume of ethanol. The bacteria were pelleted, and an aliquot of the supernatant was diluted with ethanol and dextran was precipitated. The supernatant was removed and the precipitate was dissolved in a minimal volume of water. Activated charcoal was added and the solution was boiled. The solution was filtered and protein impurities removed by 2-methylbutan-2-ol/chloroform extraction. Dextran was again precipitated with cold ethanol as described above, and the precipitate was dried in a desiccator. Optimum conditions and composition of culture media for dextran production using sugar-beet molasses and wheat bran were determined. The best results were obtained when 20% (w/v) molasses and 15% (w/v) wheat bran were used. The optimal initial pH for dextran production was 7.5.

Bioreactors↗

The role of intravenous administration of dextran 70 in enteric bacterial translocation after partial hepatectomy in rats.

The aim of this study was to assess the effect of intravenous dextran on bacterial translocation and intestinal vascular endothelial and epithelial barrier function after experimental partial hepatectomy. We determined systemic arterial pressure, enteric bacterial growth (proximal and distal small intestine and colon) and bacterial translocation (BT) to mesenteric lymph nodes (MLN), liver, lungs, spleen, kidneys and blood, as well as intestinal vascular endothelial and epithelial barrier permeability, after sham operation or partial hepatectomy (50% and 90%) with preoperative intravenous administration of saline, albumin or dextran 70. Subtotal hepatectomy induced a significant decrease in arterial pressure and an increase in the number of Escherichia coli in the distal small intestine. BT was not observed in sham-operated animals or in rats with 50% hepatectomy administered dextran. The number of positive cultures of enteric bacteria was significantly increased after hepatectomy, whereas dextran treatment decreased the number of animals with BT. Increased permeability of the intestinal vascular endothelial and epithelial barriers was noted in hepatectomized animals, while dextran prevented hepatectomy-induced vascular endothelial barrier injury. Enteric bacterial translocation occurred following partial hepatectomy in the rat, associated with bacterial overgrowth in the distal small intestine. Intravenous administration of dextran 70 prevented bacterial overgrowth and translocation, at least in part, by maintaining gut vascular endothelial barrier integrity

Animals↗

Chronic peritoneal dialysis in iron-deficient rats with solutions containing iron dextran.

BACKGROUND: We evaluated the effects of different concentrations of iron dextran administered through the intraperitoneal route, in iron-deficient rats, on hematocrit (Hct in percentage), serum iron (mg/dL), total iron binding capacity (TIBC in mg/dL), and the function and histology of the peritoneal membrane. METHODS: Seventy-two male Sprague-Dawley rats weighing 85 to 110 g were divided into two groups and seven subgroups. Group I consisted of rats on iron-deficient chow, and group II consisted of rats on normal chow. Both groups contained dialysis control subgroups (N = 12: IA, IID), dialyzed with Dianeal solution, and tissue control subgroups (N = 6: IE, IIN), in which rats were not dialyzed and catheters were not implanted. Study group I contained the following study subgroups (N = 12): (B) rats dialyzed with Dianeal solution containing 2 mg/L of iron dextran and (C) rats dialyzed with Dianeal solution containing 1 mg/L of iron dextran. Group IID was dialyzed with Dianeal solution containing 2 mg/dL of iron dextran. Study duration was 12 weeks with peritoneal equilibration tests (PETs) performed at baseline, 6 weeks, and 12 weeks. Prior to baseline, rats were placed on iron-deficient chow or normal chow for three weeks. Dialysis was performed with three 25 mL volume exchanges per day. Hematocrit (Hct), serum iron (Fe), and total iron binding capacity (TIBC) were determined for each study interval. After the final PET, the animals were sacrificed, and the peritoneal membrane was evaluated by gross inspection and light microscopy. RESULTS: Rats on an iron-deficient diet developed severe iron-deficiency anemia after three weeks of the diet (Hct 27; Fe 21 to 23; TIBC 799 to 806). After 12 weeks, the rats remained anemic in groups A (Hct 34 +/- 0.9; Fe 16 +/- 2; TIBC 998 +/- 27) and IE (Hct 38 +/- 2.7), whereas the rats corrected anemia in group B (Hct 45.8 +/- 1.8; Fe 115 +/- 15; TIBC 546 +/- 77). The results were not significantly different from those of group IID (Hct 47.1 +/- 1.6; Fe 94 +/- 19; TIBC 516 +/- 46). In group C, Hct (44.8 +/- 2.1) and Fe (94 +/- 19) did not differ significantly from group IID, but TIBC (734 +/- 76) remained significantly higher than that in the group IID. Peritoneal iron deposits were not detected. The morphometric analysis of the submesothelial space did not reveal any difference in thickness between dialysis groups. PETs were not significantly different among groups. CONCLUSIONS: Intraperitoneal iron dextran supplementation in concentrations of 2 mg/L of dialysis solution is nontoxic to the peritoneum and effective in correcting iron deficiency in rats maintained on an iron-deficient diet. Iron dextran in concentration of 1 mg/L of dialysis solution may be sufficient for correcting a lesser degree of iron deficiency.

Animals↗

A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common disorder in patients with end-stage renal disease (ESRD) that causes motor agitation and insomnia. Because RLS has been associated with iron deficiency, we sought to investigate the effects of intravenous (IV) iron dextran on symptoms of RLS in a double-blind placebo-controlled trial. METHODS: Patients determined to have RLS by International RLS Study Group criteria were administered either iron dextran, 1,000 mg, or normal saline IV in a blinded fashion. Patient demographic data were collected, and blood chemistry tests, liver function studies, serum iron levels, ferritin levels, and total iron-binding capacity were obtained at baseline and 1, 2, and 4 weeks postinfusion. Side effects or adverse events to interventions were monitored, and RLS symptoms were assessed by a rating scale at the same intervals. RESULTS: Eleven patients were randomly assigned to the administration of iron dextran, and 14 patients to the administration of saline. RLS severity scores were slightly higher in the placebo group at baseline, but hemoglobin levels, iron stores, and other biochemical parameters did not differ. Although no change in symptoms were seen in the placebo-treated group, significant improvement in RLS symptom scores in response to iron dextran was seen 1 week after infusion (-2; interquartile range [IQR], -6 to -1; P = 0.03, Wilcoxon's rank sums), but was greatest at 2 weeks (-3; IQR, -5 to -2 compared with -1 to 0; P = 0.01). Salutary effects of iron persisted at 4 weeks, but were no longer statistically significant. The significant increase in serum ferritin levels and iron saturation observed in the iron dextran-treated group was not seen in the placebo-treated group. No differences in adverse events were noted between groups. CONCLUSION: High-dose iron dextran infusion is associated with a significant, but transient, reduction in symptoms of RLS in patients with ESRD.

Adult↗

The beneficial effect of dextran on anastomotic patency and flap survival in a strongly thrombogenic model.

Dextran lowers the probability of thrombus formation, by reducing platelet aggregation and adhesion and by increasing fibrinolysis. All studies to date using dextran for microvascular reconstruction have examined only short-term (1 to 2 hr) patency in isolated vessels. The current study used an established thrombotic model (inverted sleeve interposition graft), to investigate the effect of dextran on the long-term survival of pedicle flaps. A6- x 3-cm epigastric flap was elevated. A 2-mm inverted sleeve interposition graft was placed on the artery side of the pedicle by microvascular techniques. One group received dextran (17 cc/kg) 2 hr preoperatively and every 6 hr postoperatively for the next 72 hr. A control group received saline on the same schedule. Survival was assessed on postoperative day 7, at which time necrosis was obvious. Several parameters (clotting studies and electron microscopy) were studied to characterize the phenomenon more clearly. Only 25 percent of saline-treated flaps survived (2/8), while all dextran-treated flaps survived (7/7) (p less than 0.02, Fisher exact test). Thus, dextran allowed flaps to survive by preventing thrombus formation, despite a strong thrombogenic focus.

Animals↗

The role of fetal breathing motions compared with gasping motions in pulmonary airway uptake of intra-amniotic iron dextran.

OBJECTIVE: We hypothesized that normal fetal breathing, not acute asphyxial gasping, results in the movement of iron dextran from the amniotic cavity into the fetal lungs. In addition, the amount of iron dextran moving into the fetal lungs is cumulative with time. STUDY DESIGN: Twelve pregnant New Zealand White rabbits at 25 days of gestation were sedated and underwent ultrasound-guided injections of iron dextran into the amniotic cavities of the rabbit fetuses in both horns of each pregnant doe. Oxygen saturation was maintained at >90% in the pregnant does. The 12 does were then equally assigned to four groups on the basis of the duration of fetal exposure to the dextran (0, 8, 16, and 24 hours). At the end of each time point, one half of the fetuses received an intracardiac injection of potassium chloride to induce gasping just before necropsy. Gasping was confirmed by ultrasound scanning. At necropsy, the fetal lungs were evaluated grossly and underwent histomorphometry for iron distribution and quantification in the fetal airways. RESULTS: In the animals that received iron dextran, there was no significant difference in iron accumulation at any time point between those animals that did and did not receive potassium chloride, which suggests that acute gasping does not increase the accumulation of amniotic fluid substances in the lungs. The amount of iron in the fetal airways increased significantly with progressive length of exposure. CONCLUSION: We conclude that normal fetal breathing, not acute asphyxial gasping, resulted in the movement of intra-amniotic iron dextran into the fetal lungs and that the amount of substances that move into the fetal lungs accumulated with time.

Amniotic Fluid↗

Antigen-induced strain-specific autoantiidiotypic antibodies modulate the immune response to dextran B 512.

Sera from CBA and C57BL mice immunized against dextran B 512 eight or more days earlier contain mainly IgG antibodies that specifically suppress the development of plaque-forming cells against dextran in vitro. Suppression was not caused by antibodies against the alpha 1-6 epitope of dextran to any major extent. Sera from CBA mice (IgCH allotype j) suppressed plaque-forming cells from CBA mice, whereas sera from C57BL mice (allotype b) inhibited plaques from C57BL and CBA/Ig-1b mice. Sera from dextran-tolerant mice or from mice that are genetic unresponders to dextran did not suppress plaque-forming cells. Both thymus-independent and thymus-dependent forms of dextran induced the appearance of these autoantiidiotypic antibodies that can distinguish between anti-alpha 1-6 antibodies produced in mouse strains having different IgCH-locus-determined allotypes.

Animals↗

Phytate technetium-99m versus dextran 500 technetium-99m in the sentinel lymph node biopsy.

PURPOSE: To study which of the two most used radiopharmaceutical drugs for the sentinel lymph node (SLN) biopsy procedure (dextran 500 99mTc and phytate 99mTc) best defines the SLN and migrates less to other lymph nodes. MATERIAL AND METHODS: Thirty-two rats, separated into two groups, underwent lymphoscintigraphy examination with either dextran or phytate followed by sentinel (popliteal), lumbar, and inguinal lymph node biopsy. Radiation was detected with a gamma probe. RESULTS: The statistical study indicated count rates significantly higher in the SLN than in the other basins for both the dextran (P<0.01) and phytate groups (P<0.001). There was no statistically significant difference concerning SLN absorption in either group (P=0.2981). In the dextran group, migration occurred to 1.5 lymphatic basins with counting higher than 10% of that found in the SLN versus 0.8 in the phytate group (P=0.0023). Migration was thus higher in the dextran group (P=0.0207). CONCLUSION: There was no statistically significant difference between dextran and phytate in the SLN identification, but the phytate migrated to fewer lymphatic basins beyond the SLN and with less intensity.

Animals↗

Reduction mammaplasty and the use of dextran against thromboembolism.

A retrospective study was conducted on 98 consecutive patients who had reduction mammaplasty done by different techniques during 1995, to find out the effect of dextran 70 on operative blood loss and postoperative complications. The most common procedure was reduction with a laterally based flap (n = 67) followed by a Lejour vertical mammaplasty (n = 15) and a medially based flap (n = 12). Four had other operations. Dextran 70 was given peroperatively to 64 patients and their median (range) blood loss was 350 (30-1000) ml and drainage volume 80 (10-465) ml. In 33 patients not treated with dextran 70 the median (range) blood loss was 200 (25-650) ml and the drainage volume 40 (0-115) ml. Ten patients developed major complications and 16 minor complications and there was no difference in the complication rate between those given dextran 70 (18/64, 28%) and those who were not (8/33, 24%), p = 0.8. Complications were no more common in smokers, overweight patients or those whose breasts were reduced by more than 1500 g, but there was a tendency to find more complications after the Lejour vertical mammaplasty. In conclusion, the study shows that patients undergoing mammaplasty and given Dextran 70 have an acceptable blood loss and drainage. In patients with a high risk of developing thromboembolism there is a need for a prophylactic agent and this study shows that dextran 70 may safely be used during reduction mammaplasty.

Adolescent↗

Synthesis and properties of dextran-linked ampicillin.

Ampicillin was coupled to dextran of average molecular weight 9,000 or 81,200 via the cyanogen bromide method. The degree of drug substituted per glucose unit (DSG) was varied from 0.104 to 0.028 (by weight bases: 22.1-5.9%) depending on the ratio of the reactants. Water solubility of dextran-linked ampicillin increased compared with free ampicillin, and the solubility decreased as the amount of ampicillin substituted increased. Plasma concentration of ampicillin, which appeared after intravenous administration of dextran-linked ampicillin in rats, was higher than when free ampicillin was administered, and the more so, the higher the molecular weight of dextran. Plasma half-life of dextran-linked ampicillin was two times longer than that of free ampicillin in rats. Antibacterial activities of dextran-linked ampicillin were evaluated against Staphylococcus aureus, Bacillus substillis, and Escherichia coli at two concentration levels according to the cup-plate method by measuring the diameter of inhibition zone, which was comparable to that of free ampicillin.

Ampicillin↗

The effects of aerosolized dextran in a mouse model of Pseudomonas aeruginosa pulmonary infection.

Airway infections initiated by the interaction of bacterial adhesins with carbohydrate receptors can be potentially prevented by nontoxic carbohydrate inhibitors. Intranasal inoculation of neonatal mice with Pseudomonas aeruginosa PAO1 caused pneumonia in 55% of control mice but in only 13% of mice inoculated 2 h after dextran inhalation (P<.001) and in 28% inoculated 4 h after dextran inhalation (P=.02). PAO1 adherence to epithelial cells was inhibited by 50% in the presence of dextran. Dextran was well distributed throughout the airways and stimulated tumor necrosis factor-alpha production in murine lungs but not interleukin-8 production by human epithelial cell lines. Phagocytosis of PAO1 was not affected by dextran nor was killing by human neutrophils diminished. Administration of dextran by aerosol may prevent murine pneumonia by impeding bacterial access to epithelial receptors and by stimulation of the immune functions of the epithelium.

Aerosols↗

The effect of iron dextran on ferritin content and 131I-antiferritin localization in experimental hepatomas.

Polyclonal 131I rabbit antirat ferritin localizes in certain hepatoma models. The effect of intraperitoneal iron dextran on tumor and sera ferritin content and tumor and normal tissue localization with 131I antiferritin was studied. Separate groups of 10-12 animals were injected with escalating doses of 131I-antiferritin IgG, or nonspecific IgG, one week after injection with iron dextran or normal saline. The results demonstrate that tumor, serum, and normal tissue ferritin content was increased after iron dextran administration but tumor localization increased after administration of 131I-antiferritin in the H4II-E and 7800 models. The 3924A and 7777 models showed no tumor localization with or without iron dextran but did show an increase in normal tissue localization after iron dextran. Immunoperoxidase staining of tissues with antiferritin revealed increased staining in the liver and spleen and only a slight increase in the tumors after iron dextran was administered. The results demonstrate that tumor localization is a complex phenomenon that depends on normal tissue, sera, and tumor-antigen distribution.

Animals↗

SIGN-R1, a novel C-type lectin expressed by marginal zone macrophages in spleen, mediates uptake of the polysaccharide dextran.

The marginal zone macrophages of the spleen are implicated in the clearance of polysaccharides, but underlying mechanisms need to be pinpointed. SIGN-R1 is one of five recently identified mouse genes that are homologous to human DC-SIGN and encode a single, external, C-terminal C-type lectin domain. We find that a polyclonal antibody to a specific SIGN-R1 peptide reacts primarily and strongly with a subset of macrophages in the marginal zone of spleen and lymph node medulla. In both sites, SIGN-R1 exists primarily in an aggregated form, resistant to dissociation into monomers upon boiling in SDS under reducing conditions. Upon transfection into three different cell lines, high-mol.-wt forms bearing SIGN-R1 are expressed, as well as reactivity with ER-TR9, a mAb previously described to react selectively with marginal zone macrophages. SIGN-R1-expressing macrophages preferentially sequester dextrans following i.v. injection. Likewise, when phagocytic cells are enriched from spleen and tested in culture, dextran is selectively endocytosed by a subset of very large SIGN-R1(+) cells representing approximately 5% of total released macrophages. Uptake of FITC-dextran by these macrophages in vivo and in vitro is blocked by ER-TR9 and polyclonal anti-SIGN-R1 antibodies. Following transfection with SIGN-R1, cell lines become competent to endocytose dextrans. The dextran localizes primarily to compartments lacking transferrin receptor and the LAMP-1 CD107a panlysosomal antigen. Therefore, SIGN-R1 mediates the uptake of dextran polysaccharides, and it is predominantly expressed in the macrophages of the splenic marginal zone and lymph node medulla.

Animals↗

Higher antitumor efficacy of daunomycin when linked to dextran: in vivo and in vitro studies.

Daunomycin was coupled to dextrans of various molecular sizes. The binding to the dextran carriers augmented the therapeutic efficacy of the antitumor agent in a murine lymphoma line (YAC). When the treatment with the drug or its conjugates was given concomitantly with the tumor cells at separate sites, the unbound drug was able, at its optimally effective doses, to prevent tumors in 40% of the mice, whereas the drug-dextran was efficient in 80% of the mice. The advantage of the drug-dextran over the free drug was also manifested when the treatment was given 6 days after tumor transplantation. However, a further delay of the treatment resulted in a decrease in the potency of the drug-dextran. Similar behavior was observed when increasing tumor loads were transplanted (10(5)-10(8) cells) and when the treatment was administered immediately. The most favorable effect of the drug-dextran was obtained with 10(7) cells, but against 10(8) cells neither the free drug nor the bound one was effective.

Animals↗