Molecular Weight Dextran Research Articles

Spray drying of silica microparticles for sustained release application with a new sol-gel precursor

A new precursor, tetrakis(2-methoxyethyl) orthosilicate (TMEOS) was used to fabricate microparticles for sustained release application, specifically for biopharmaceuticals, by spray drying. The advantages of TMEOS over the currently applied precursors are its water solubility and hydrolysis at moderate pH without the need of organic solvents or catalyzers. Thus a detrimental effect on biomolecular drug is avoided. By generating spray-dried silica particles encapsulating the high molecular weight model compound FITC-dextran 150 via the nano spray dryer Büchi-90, we demonstrated how formulation parameters affect and enable control of drug release properties. The implemented strategies to regulate release included incorporating different quantities of dextrans with varying molecular weight as well as adjusting the pH of the precursor solution to modify the internal microstructures. The addition of dextran significantly altered the released amount, while the release became faster with increasing dextran molecular weight. A sustained release over 35days could be achieved with addition of 60 kD dextran. The rate of FITC-Dextran 150 release from the dextran 60 containing particles decreased with higher precursor solution pH. In conclusion, the new precursor TMEOS presents a promising alternative sol-gel technology based carrier material for sustained release application of high molecular weight biopharmaceutical drugs.

The effect of dextran molecular weight on the biodegradable hydrogel with oil, synthesized by the michael addition reaction

Plant oil and derivatives have been used in polymer biomaterials, especially as starting materials for the synthesis of bio-based polymers. The uses have many advantages such as biodegradability, renewability, energy saving, easy of production, less CO2 emission, and low price. Hydrogels were prepared from natural materials: acrylate-epoxidized soybean oil and dextran. The effects of temperature, reaction time, and molar ratios of the reactants were examined on acrylation of dextran of the hydrogel. The dextran acrylates were tested for their solubility and characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance. Hydrogels were characterized by FT-IR. The pore sizes of hydrogels were examined by scanning electronic microscopy. Also, swelling tests were performed on hydrogels. The new biodegradable hydrogels were formed from dextran and different molecular weights of acrylate-epoxidized soybean oil, by the Michael addition reaction using pentaerythritol tetrakis(3-mercaptopropionate) (QT) and triethylamine as catalyst at 30/70 composition.

Amphipathic dextran-doxorubicin prodrug micelles for solid tumor therapy

A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH2) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH2. These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX. After optimization, Dex10k-DCA9-DOX5.5 conjugate comprising dextran of 10kDa, DCA of DS 9 and DOX loading content of 5.5wt%, formed the micelles with the smallest size (110nm). These prodrug micelles could slowly liberate DOX under physiological conditions but efficiently released the drug at an acidified endosomal pH by the hydrolysis of acid-labile hydrazone linker. In vitro cytotoxicity experiment indicated that Dex10k-DCA9-DOX5.5 micelles exerted marked antitumor activity against MCF-7 and SKOV-3 cancer cells. Besides, intravenous administration of the micelles afforded growth inhibition of SKOV-3 tumor bearing in nude mice at a dosage of 2.5mg per kg with anti-cancer efficacy comparable to free DOX-chemotherapy but low systemic toxicity. This study highlights the feasibility of bio-safe and efficient dextran-based prodrug micelles designed for cancer chemotherapy.

Improved Dextranase Production by Chaetomium gracile Through Optimization of Carbon Source and Fermentation Parameters

The fungus Chaetomium gracile is used for production of dextranase and removal of dextran during sugar manufacturing process, however, the productivity of dextranase is low. In this study, we investigated the influence of carbon source on dextranase production using dextrans of different sizes. Culturing C. gracile in medium containing crude dextran and use of high molecular weight of dextrans resulted in the higher yield of dextranase production (80.5 ± 4.0 U ml−1). Cells incubated in medium containing glucose as sole carbon source exhibited a high growth rate but did not produce dextranase. Based on these findings, fed-batch and two-step fermentation strategies were employed to further increase the yield of dextranase with production of 159.5 and 187.0 U ml−1, respectively.

Degradation of acetalated dextran can be broadly tuned based on cyclic acetal coverage and molecular weight

Microparticles (MPs) derived from acid-sensitive biopolymers enable rapid degradation and cargo release under acidic conditions, such as at tumor microenvironments, within lysosomal/phagosomal compartments inside phagocytic cells, or at sites of inflammation. One such acid-sensitive biopolymer, acetalated dextran (Ace-DEX), has tunable degradation rates and pH-neutral degradation byproducts consisting of dextran, acetone, and ethanol. By studying the degradation profiles of Ace-DEX MPs with varying cyclic acetal coverage (CAC) and dextran molecular weight (MW), we concluded that MPs composed of low CAC or high MW polymer degraded the fastest at both pH 7.4 and 5.0. To further understand the properties of this unique polymer, we encapsulated a model drug resiquimod, which is a toll-like receptor (TLR) 7/8 agonist, into Ace-DEX MPs of different polymer CAC and dextran MW. It was observed that resiquimod was released faster from MPs of lower CAC or higher MW. By evaluating the activation of RAW macrophages cultured with different types of resiquimod-loaded Ace-DEX MPs, we found that MPs of lower CAC or higher MW promoted greater nitrite production and resulted in more robust cell activation. Our results indicate we can precisely control the degradation profile, release kinetics, and bioactivity of encapsulated cargos by altering CAC and MW, furthering Ace-DEX MPs' novelty as a drug carrier.

A microfluidic platform with permeable walls for the analysis of vascular and extravascular mass transport

The interface between the blood pool and the extravascular matrix is fundamental in regulating the transport of molecules, nanoparticles and cells under physiological and pathological conditions. In this work, a microfluidic chip is presented comprising two parallel microchannels connected laterally via an array of high aspect ratio micropillars, constituting the permeable vascular membrane. A double-step lithographic process combined with a replica molding approach is employed to realize 80 different arrays of micropillars exhibiting three cross-sectional geometries (rectangular, elliptical and curved); two orientations (normal and parallel) with respect to the flow; and a variety of width and gap sizes, respectively, ranging from 10 to 20 μm and 2 to 5 μm. As compared to conventional rectangular structures, the curved pillars provide higher bending stiffness, lower adhesive interactions, and smaller intra-channel separation distances. Specifically, 10-μm-wide curved pillars, laying parallel to the flow, offered the highest mechanical stability. To assess vascular permeability, the extravascular channel was filled with a hyaluronic acid hydrogel, while fluorescent Dextran molecules and calibrated polystyrene beads were injected in the vascular channel. Membrane permeability was observed to reduce with the molecular weight of Dextran and diameter of the beads, ranging from about 6 × 10−5 to 2 × 10−5 cm/s for 40 and 250 kDa Dextran and up to zero for 1.5 μm beads. The presented data demonstrate the potential of the proposed microfluidic chip for analyzing the vascular and extravascular mass transport, over multiple spatial and temporal scales, in a variety of diseases involving differential permeation across vascular walls.

Biosynthesis of oleyl oleate in solvent-free system by Candida rugosa Lipase (CRL) immobilized in macroporous resin with cross-linking of aldehyde-dextran

In our study, oleyl oleate was synthesized through enzymatic esterification of oleic acid with oleyl alcohol using Candida rugosa lipase (CRL) immobilized on macroporous resin in a solvent-free system. CRL was immobilized flexibly on the support via aldehyde-dextran, and the effectiveness of aldehyde-dextrans, as cross-linking agents with different molecular weights, was compared and discussed. The impact of various factors, such as different molecular weights of dextran, molar ratio between oleic acid and oleyl alcohol, and the temperature and stability of enzymes, on esterification was investigated as well. Our study indicated that lipase immobilized by 20000Da dextran yielded the best result. The optimal condition to produce oleyl oleate using immobilized CRL was found in our study and turned out to be molar ratio of 1, reaction temperature of 40°C, and a 12-h reaction time to reach reaction equilibrium. Under the optimal reaction conditions, a high percentage yield of ester was achieved (92.6%). The immobilized CRL also reached a conversion rate of 86.7% with excellent stability even after 8 cycles.

The combined application of low molecular dextran, papaverine and low molecular weight heparin sodium to improve testicle survival rate after the reduction of testicular torsion in rabbits

Objective To observe the effect of drug combinations on the blood flow after reduction of the testicular torsion in rabbits. Methods From October 2014 to June 2015, 36 male rabbits(weighing 1.8-2.4 kg, 10-14 months of age) were randomly divided into experimental group and control group, 18 in each group.Produced by surgical testicular torsion model (720°counterclockwise rotation of the left side testicle), every rabbit was accepted surgery reset after 9 hours and found all twisted testicles were dark.After fomentation with warm salt water, all the testicles were observed no significant improvement in colors, and no fresh blood flow after opening tunica albuginea, then all the testicles were retained and fixed.Low molecular dextran(5 ml/kg, ear marginal vein injection, 1/d), papaverine(1.5 mg/kg, intramuscular, 3/d) and low molecular weight heparin sodium(200 IU/kg, subcutaneous, 1/d) were applied to promote testicular revascularization for 5 days in experimental group, and penicillin (40 000 U/kg, intramuscular, 1/d) for 7 days.Control group was only given penicillin(40 000 U/kg, intramuscular, 1/d) to prevent wound infection.Then Color Doppler ultrasound was used to observe the testicular blood flow siganals that were divided into 0, 1, 2, 3 classes.Class 2 and class 3 could be considered as testicular survival.After each scrotum was opened, according to color, texture of testicle and whether the fresh blood flowing out when tunica albuginea was opened, to determine whether the testicle was alive.The testicle was ruddy, flexible, and fresh blood was observed, which could prove testicular survival. Results In experimental group, the testicular blood flow siganals: 0 class 4 cases, 1 class 3 cases, 2 class 4 cases, 3 class 7 cases.In control group, the testicular blood flow siganals: 0 class 9 cases, 1 class 2 cases, 2 class 4 cases, 3 class 3 cases.Surgical exploration found 11 cases of testicular survival in experimental group and 7 cases in control group, which was significantly difference (P<0.05). Conclusions The combined application of low molecular dextran, papaverine, low molecular weight heparin sodium can promote the recovery of testicular blood after reduction of testicular torsion, and improve testicular survival rate. Key words: Testicular torsion; Low molecular dextran; Papaverine; Low molecular weight heparin sodium; Testicular survival

Monitoring the Effect of the Dextran Molecular Weight on Sucrose Crystallization by Focused Beam Reflectance Measurement (FBRM)

The influence of the molecular weight of dextran on the crystallization of sucrose (including primary and secondary crystallization) in a pure sucrose solution was investigated via in-line focused beam reflectance monitoring. The most pronounced effect of dextran on sucrose crystallization was found with molecular weights >500,000 at a concentration of 2500 ppm. Molecular weight of 6000 has no profound effect on sucrose crystallization under the same condition. The results demonstrated that high molecular weight dextran delays and reduces the primary crystallization rate of sucrose and enlarges the unweighted chord length distribution zone.

Diffusion Properties of Cardiac T-Tubular System

Action potentials (APs), via the transverse axial tubular system (TATS), synchronously trigger uniform Ca2+ release throughout the cardiomyocyte. In cardiomyocytes from diseased hearts we previously documented the presence of TATS elements which failed to propagate AP (Sacconi et al. PNAS 2012). Using an imaging method to simultaneously assess TATS electrical activity and local Ca2+ release we recently demonstrated that failing tubular elements show a slower local Ca2+ transient compared with regions with electrically coupled elements (Crocini et al. PNAS 2014). The causes of AP propagation failure remained, however, unsolved. TATS structural remodelling that is generally associated with pathological settings may increase the tubular electrical resistance, augmenting the probability that the depolarization wavefront fails in reaching the AP threshold at the tubular membrane. TATS structural changes can modify the diffusion properties of T-tubule lumen. Here, we used fluorescence recovery after photo-bleaching (FRAP) microscopy to probe the diffusion properties of TATS lumen in cardiomyocytes. T-tubules of isolated cardiomyocytes from rodent models of cardiac diseases are labelled using fluorescent dextran that diffuses from extracellular space to TATS lumen. The fluorescent dextran present inside TATS lumen is photo-bleached and the diffusion of unbleached dextran from extracellular space to TATS is monitored using confocal imaging. Analysing the recovery of the fluorescence signal at pixel-by-pixel level, a diffusional map of the tubular system is obtained. Diffusion maps performed at different dextran molecular weight are acquired to probe structural features of the TATS lumen. Finally, diffusion maps in different pathological models are reconstructed to find potential mechanisms for the presence of AP failing TATS elements.

Diffusion of macromolecules in a polymer hydrogel: from microscopic to macroscopic scales.

To gain insight into the fundamental processes determining the motion of macromolecules in polymeric matrices, the dynamical hindrance of polymeric dextran molecules diffusing as probe through a polyacrylamide hydrogel is systematically explored. Three complementary experimental methods combined with Brownian dynamics simulations are used to study a broad range of dextran molecular weights and salt concentrations. While multi-parameter fluorescence image spectroscopy (MFIS) is applied to investigate the local diffusion of single molecules on a microscopic length scale inside the hydrogel, a macroscopic transmission imaging (MTI) fluorescence technique and nuclear magnetic resonance (NMR) are used to study the collective motion of dextrans on the macroscopic scale. These fundamentally different experimental methods, probing different length scales of the system, yield long-time diffusion coefficients for the dextran molecules which agree quantitatively. The measured diffusion coefficients decay markedly with increasing molecular weight of the dextran and fall onto a master curve. The observed trends of the hindrance factors are consistent with Brownian dynamics simulations. The simulations also allow us to estimate the mean pore size for the herein investigated experimental conditions. In addition to the diffusing molecules, MFIS detects temporarily trapped molecules inside the matrix with diffusion times above 10 ms, which is also confirmed by anisotropy analysis. The fraction of bound molecules depends on the ionic strength of the solution and the charge of the dye. Using fluorescence intensity analysis, also MTI confirms the observation of the interaction of dextrans with the hydrogel. Moreover, pixelwise analysis permits to show significant heterogeneity of the gel on the microscopic scale.

Green Synthesis of Silver Nanoparticles: Effect of Dextran Molecular Weight Used as Stabilizing-Reducing Agent.

This paper describes an easy green chemistry method for the synthesis of silver nanoparticles (AgNPs). The AgNPs were obtained through the use of an aqueous silver nitrate solution (AgNO3), with dextrans aqueous solutions of different molecular weights acting as stabilizing and reducing agent, employing the chemical reduction method. We made a comparative study to determine which molecular weight dextran was the best stabilizing and reducing agent, and it was found that the molecular size of the stabilizing agent is inversely proportional to the size of the nanoparticle synthesized. The formation of the AgNPs was demonstrated by UV-Vis spectroscopy, atomic force microscopy (AFM), scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and transmission electron microscopy (TEM). SEM-EDS analysis shows the formation of particles with dendritic structure. TEM shows nanoparticles which are spherical in shape and 1-10 nm in size; also, the clear lattice fringes show highly crystalline AgNPs (FCC).

The Effect of Dextran Molecular Weight on the Biodegradable Hydrogel with Oil, Synthesized by the Michael Addition Reaction

The Effect of Dextran Molecular Weight on the Biodegradable Hydrogel with Oil, Synthesized by the Michael Addition Reaction

Implications of Volume Exclusion: A Look at Thermodynamic Perspective of DNA-Hemoglobin Complexes and Their Reconstitutes Under Macromolecular Crowding.

Live cells contain high concentrations of macromolecules, but almost all experimental biochemical data have been generated from dilute solutions that do not reflect conditions in vivo. To understand biomolecular behavior in vivo, properties studied in vitro are extrapolated to conditions in vivo. Another significant factor which is overlooked is the effects of macromolecular crowding and its consequences in the actual biochemical and physiological environment. Such influences of crowding, its modification and physiological parameters have been reported. The present study investigates the effect of molecular crowding on binding characteristics of Salmon sperm DNA with Bovine hemoglobin and their reconstitutes in presence of molecular crowders viz., Poly ethylene glycol (PEG) and Dextran of different molecular weight by fluorescence, UV visible spectroscopic technique at different temperatures. The results showed that BHb fluorescence was quenched by sDNA through static quenching mechanism which is enhanced in presence of polymers. The number of binding sites 'n' and binding constants 'K' were determined at different temperatures based on fluorescence quenching. The thermodynamic parameters namely ∆H°, ∆G°, T∆S° were studied at different temperatures and the results indicate that hydrophobic forces are predominant in the sDNA-BHb complex. Negative ∆G° values imply that the binding process is spontaneous.

Covalent immobilization of Enterococcus faecalis Esawy dextransucrase and dextran synthesis

Enterococcus faecalis Esawy dextransucrase was immobilized in Fe3+-cross-linked alginate/carboxymethyl cellulose (AC) beads. The gel beads were modified with polyethylenimine (PEI) followed by glutaraldehyde (GA) to form Fe3+ (ACPG) beads. Fe3+ (ACPG) was characterized using FTIR and DSC techniques. GA activated beads showed new two peaks. The first was at 1717cm−1 which refers to (CO) group of a free aldehyde end of glutaraldehyde, and another peak was at 1660cm−1 referring to (CN) group. The immobilization process improved the optimum temperature from 35 to 45°C. The immobilized enzyme showed its optimum activity in wide pH range (4.5–5.4) compared to pH 5.4 in case of free form. Also, the immobilization process improved the thermal and pH enzyme stability to great extent. Reusability test proved that the enzyme activity retained 60% after 15 batch reactions. Immobilized enzyme was applied successfully in the synthesis of oligosaccharides and different molecular weights of dextran.

PVDF/palygorskite composite ultrafiltration membranes with enhanced abrasion resistance and flux

The anti-wearing property is important to the lifetime of membranes especially when they are used in heavy-duty water treatment, where the content of suspended solid is often high. Abrasion-resistant membranes are expected to have prolonged lifetimes and reduce considerably the maintenance cost of water treatment plants. In this research, palygorskite (PGS), a natural abundant nano rod-like clay material with hydrophilic properties and excellent mechanical strength, was used as the reinforcement filler in poly(vinylidene fluoride) (PVDF) ultrafiltration membranes to improve the anti-wearing property. The prepared membranes were subjected to a series of characterisations to investigate membrane structure, surface hydrophilicity, filtration performance and mechanical strength. A simple, quantitative methodology was also proposed to assess the abrasion resistance of the membranes, aiming to establish a feasible and reliable testing protocol in the laboratory. It is found that the PGS readily improves tensile strength, Young's modulus and the abrasion resistance to SiC particles, whilst the permeability of the membranes increases without sacrificing selectivity. Particularly, the addition of 10% PGS leads to a drastic increase in abrasion resistance, with the abrasion rate reduced to 1/170 of the unreinforced membrane, which could be attributed to the transition of abrasion from a ductile manner to a brittle manner. Moreover, the 10% PGS reinforced membrane shows increased permeation flux from 106.1L/m2h to 282.5L/m2h, and the dextran molecular weight cut-off (MWCO) was maintained at a level of 150–200kDa.

The influence of cheese composition and microstructure on the diffusion of macromolecules: A study using Fluorescence Recovery After Photobleaching (FRAP)

In cheese technology, the diffusion phenomena are crucial during ripening. The technique of Fluorescence Recovery After Photobleaching was applied for the first time on real cheese, in order to investigate the relationships between molecular diffusion and the cheese composition and/or its microstructure. Measured effective diffusion coefficients in soft and hard cheese of a group of dextrans (10–500kDa) were found to be in the same order of magnitude with values observed when using a comparable non-fat model cheese (∼0.1–20μm2s−1). Diffusion of the dextrans was mainly dependent on the fraction of “free” aqueous phase present in the cheese, closely which is linked to cheese-making technology and ripening stage. Diffusion coefficients were modeled by a power law relationship as a function of dextran molecular weight, which allowed some study of the cheese microstructure. A tighter protein network will require some deformation of those flexible macromolecules with a higher molecular weight (>250kDa), in order to diffuse through the pores of such cheese structures.

Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon

Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.

Molecular weight characterization of high molecular weight dextran with multiangle light scattering in on-line and off-line mode.

This work reports the molecular weight (MW) analysis of high MW dextran using multiangle light scattering (MALS) in both chromatography and automated batch measurement mode. The results show that the chromatographic columns alter the high MW native dextran and cause underestimation of the MW as a consequence. Alternatively, a batch MALS measurement (without columns) provides more accurate MW values. The batch MALS measurement was automated with the incorporation of an automatic sample dilution and injection device. This automation reduces the sample preparation time and minimizes concentration errors introduced by manual sample dilution. To the best of our knowledge, this is the first study using an automated batch MALS in the analysis of high MW dextran.

Characterization of molecular transport in ultrathin hydrogel coatings for cellular immunoprotection.

PEG hydrogels are routinely used in immunoprotection applications to hide foreign cells from a host immune system. Size-dependent transport is typically exploited in these systems to prevent access by macromolecular elements of the immune system while allowing the transport of low molecular weight nutrients. This work studies a nanoscale hydrogel coating for improved transport of beneficial low molecular weight materials across thicker hydrogel coatings while completely blocking transport of undesired larger molecular weight materials. Coatings composed of PEG diacrylate of molecular weight 575 and 3500 Da were studied by tracking the transport of fluorescently labeled dextrans across the coatings. The molecular weight of dextran at which the transport is blocked by these coatings are consistent with cutoff values in analogous bulk PEG materials. Additionally, the diffusion constants of 4 kDa dextrans across PEG 575 coatings (9.5 × 10(-10)-2.0 × 10(-9) cm(2)/s) was lower than across PEG 3500 coatings (5.9-9.8 × 10(-9) cm(2)/s), and these trends and magnitudes agree with bulk scale models. Overall, these nanoscale thin PEG diacrylate films offer the same size selective transport behavior of bulk PEG diacrylate materials, while the lower thickness translates directly to increased flux of beneficial low molecular weight materials.