Molecular Weight Dextran Research Articles

Influence of Dextran Molecular Weight on the Physical Properties of Magnetic Nanoparticles for Hyperthermia and MRI Applications.

Dextran-coated magnetic nanoparticles are promising biocompatible agents in various biomedical applications, including hyperthermia and magnetic resonance imaging (MRI). However, the influence of dextran molecular weight on the physical properties of dextran-coated magnetic nanoparticles has not been described sufficiently. We synthesise magnetite nanoparticles with a dextran coating using a co-precipitation method and study their physical properties as a function of dextran molecular weight. Several different methods are used to determine the size distribution of the particles, including microscopy, dynamic light scattering, differential centrifugal sedimentation and magnetic measurements. The size of the dextran-coated particles increases with increasing dextran molecular weight. We find that the molecular weight of dextran has a significant effect on the particle size, efficiency, magnetic properties and specific absorption rate. Magnetic hyperthermia measurements show that heating is faster for dextran-coated particles with higher molecular weight. The different molecular weights of the coating also significantly affected its MRI relaxation properties, especially the transversal relaxivity r2. Linear regression analysis reveals a statistically significant dependence of r2 on the differential centrifugal sedimentation diameter. This allows the targeted preparation of dextran-coated magnetic nanoparticles with the desired MRI properties. These results will aid the development of functionalised magnetic nanoparticles for hyperthermia and MRI applications.

Aqueous two-phase systems based on thermo-separating copolymer for partitioning of doxorubicin

Copolymers have high potential for using in aqueous two-phase systems (ATPSs) due to their tunable physico-chemical properties. In this work, the phase behavior and the application of dextran – (PEG-PPG) random copolymer (UCON) ATPS for partitioning of doxorubicin were studied. Merchuk, Guan and the modified Guan relations were used to correlate the binodal experimental data. The effect of pH, molecular weight of dextran, weight fractions of UCON and NaCl as an additive on the partitioning of doxorubicin was investigated. Increasing the dextran molecular weight increased the partition coefficient, while pH had no significant effect on it. An enhancement of the weight fraction of UCON in the feed increases the partition coefficient of doxorubicin. NaCl in these ATPSs causes an increase in partition coefficient; however, NaCl concentration has no significant effect on partitioning of doxorubicin. This shows that electrostatic interaction is not the overcoming factor in the partitioning of doxorubicin. Besides, the interactions among the components in the studied aqueous two-phase systems were studied applying the Flory-Huggins parameter. It should be mentioned that the Flory-Huggins parameter was determined by the Hansen solubility parameter.

Conductive poly(2-ethylaniline) dextran-based hydrogels for electrically controlled diclofenac release.

Transdermal drug delivery systems (TDDS) are used as an alternative route to deliver drugs into the blood system for therapy. The matrix materials that have been widely used in TDDS are hydrogels. The dextran hydrogels were prepared by the solution casting using trisodium trimetaphosphate (STMP) as the crosslinking agent, and diclofenac sodium salt (Dcf) as the anionic model drug. Poly(2-ethylaniline) (PEAn) was successfully synthesized and embedded into the dextran hydrogel as the drug encapsulation host. The in-vitro release of Dcf from the hydrogels was investigated using a modified Franz-Diffusion cell in a phosphate-buffered saline (PBS) solution at the pH of 7.4 and at 37°C for a period of 24h, under the effects of crosslinking ratios, dextran molecular weights, electric potentials, and the conductive polymer PEAn. The release mechanism of Dcf from the dextran hydrogels and the composite without electrical potential was the diffusion controlled mechanism or the Fickian diffusion. Under applied electrical potentials, the release mechanism was a combination between the Fickian diffusion and the matrix swelling. The Dcf diffusion coefficients from the dextran hydrogels without electrical potential increased with decreasing crosslinking ratio and molecular weight. Under electrical potentials, the corresponding diffusion coefficients were much higher due mainly to the electro-repulsive force between the negatively charged electrode and the negatively charged dextran and the induced dextran expansion. For the Dcf-loaded PEAn/dextran composite, the diffusion coefficient was enhanced by two orders of magnitude when the electric potential was applied, specifically illustrating the unique features of PEAn as an efficient drug encapsulation host without electric field, and as a drug release enhancer under electric field through the reduction reaction.

Preparation of dextran cryogels for separation processes of binary dye and pesticide mixtures from aqueous solutions

AbstractWe present mechanically strong macroporous, squeezable dextran cryogels as a column filling material for the removal and separation of binary organic dye and pesticide mixtures from aquatic medium. Dextran cryogels were prepared from aqueous solutions of dextran of various molecular weights (MWs) in the presence of 20 to 50 mol% divinyl sulfone (DVS) as a cross‐linker at −18°C. The cryogels have interconnected irregular pores of 100 μm in sizes, and exhibit 69‐84% reversible squeezability without damaging the 3D dextran network. Their total open pore volumes (6.3‐10 mL g−1), weight swelling ratios in water (1380%‐2200%), and mechanical parameters could easily be adjusted by both DVS mol% and MW of dextran. Dextran cryogel with the highest modulus (3.8 ± 0.5 MPa), compressive stress (8 ± 2 MPa) and plateau stress (0.46 ± 0.04 MPa) was obtained at 50 mol% DVS using dextran with a MW of 15 to 25 kg·mol−1. Dextran cryogels are hydrolysable at pH = 1 and 9 but stable at 7.4 independent on both the degree of cross‐linking and MW of dextran. At below 50 mol% DVS, they are blood compatible and possess slight thrombogenic effect with blood clotting index value of 98% ± 5%. They are also capable to separate binary dye and pesticide mixtures from aqueous solutions via ionic interactions.

P0542EVALUATION OF BLOOD CELL ADHESION AND SOLUTE REMOVAL PERFORMANCE BY AN EX VIVO EXPERIMENT OF A POLYSULFONE HEMOFILTER USING AN NV POLYMER MEMBRANE FOR CONTINUOUS RENAL REPLACEMENT THERAPY

Abstract Background and Aims Since hemofilters used for continuous renal replacement therapy (CRRT) come in prolonged contact with blood during treatment, clotting and cell adhesion induced by contact of blood with the membrane often occur, increasing the risk to the patient and burden on the staff. Suppressed platelet adhesion and better biocompatibility have been reported with the use of a dialysis membrane whose surface has been modified with an NV polymer in patients on maintenance hemodialysis. Therefore, it may be advantageous to use the NV membrane as a hemofilter for CRRT. In the present study, we evaluated the solute removal performance change and blood cell adhesion on the NV membrane after it comes in contact with blood, to clarify the characteristics of the NV membrane for long-time use. Methods A new polysulfone membrane containing the NV polymer (SNV) and a conventional polysulfone membrane (SHG) were used for the ex vivo blood filtration experiment. To compare the solute removal performance change and blood cell adhesion after blood comes in contact with the membranes, porcine blood collected from a single animal was divided into two portions, and a 24-hour of continuous hemofiltration (CHF) experiment was performed. The circulation conditions were as follows; blood flow rate, 100 mL/min; filtrate flow rate, 20 mL/min; heparin dose adjusted as appropriate to maintain the activated clotting time from 300 to 400 sec during the experiment. We evaluated the time-courses of the transmembrane pressure (TMP) and pressure drop at the hemofilter and the change in the sieving coefficients of dextran of different molecular weights (molecular weight cutoff curve) before and after the experiment, and blood cell adhesion. The amount of blood cell adhesion was evaluated based on the hemoglobin content and lactate dehydrogenase (LDH) activity in the eluate from the residual blood clots on the hemofilter 24 hours after the CHF experiment. Results The changes in the TMP and the pressure drop were significantly lower with the use of SNV as compared to SHG (n = 9, p < 0.01). From the molecular weight cutoff curves before and after the experiment, the molecular weights when the sieving coefficient was 0.1 to 0.4, which reflect the pore size of the pores through which relatively small molecules can pass, decreased to a lower extent after blood contact with SNV as compared to SHG (n = 3, SC = 0.1-0.3, p < 0.05; SC = 0.4, p < 0.01).The hemoglobin content and LDH activity in the blood clots adhering to the membrane after the experiment were significantly lower in SNV as compared to SHG (n = 9; Hb, p < 0.01; LDH, p < 0.05), indicating that blood cell adhesion on SNV was less pronounced than that on SHG. Conclusion SNV suppressed the increase in the TMP and also the pressure drop, allowed a high rate of solute removal performance to be maintained, and suppresses blood cell adhesion to a greater extent as compared to the conventional polysulfone membrane.

The impact of soy protein isolate-dextran conjugation on capsicum oleoresin (Capsicum annuum L.) nanoemulsions

The purpose of this study was to conduct an in-depth investigation of the effects of soy protein isolate (SPI)-dextran (molecular weights 10, 40, 70, and 150 kDa) bonding on physical properties and environmental stability of oil-in-water emulsions containing capsaicin. Results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform-infrared (FT-IR) spectroscopy confirmed that SPI covalently links to dextran in dry-heated Maillard reactions (60 °C and 79% relative humidity). Dextran and SPI have the maximum conjugation yield at a molecular weight of 40 kDa. The capsaicin nanoemulsions were prepared using a high-pressure homogenization method with native SPI, the SPI-Dex mixture, and conjugates in an aqueous phase, and oleoresin capsicum in an oil phase. The mean particle diameter (Dz) of the capsaicin nanoemulsions stabilized by the SPI-Dex conjugates was significantly lower than that stabilized by SPI and the SPI-Dex mixture, particularly at 40 kDa. The pH, thermal stability, and storage stability of the capsaicin nanoemulsions stabilized by the SPI-Dex (40 kDa) conjugate were markedly improved and no appreciable creaming or flocculation was observed at 25 °C or 50 °C for 30 days. We concluded that the SPI-Dex conjugates formed by covalent bonding improved the physical stability of the nanoemulsion, which depended on the molecular weight of dextran. These results provide new insight into preparing highly stable nanoemulsions with good encapsulation efficiency.

Modification of myofibrillar protein via glycation: Physicochemical characterization, rheological behavior and solubility property

Functionalities of muscle protein are vital in the qualitative characteristics of final products. Glycation was explored as a promising way for upgrading the functionalities of muscle protein. Myofibrillar protein (MP) was conjugated with dextran (DX) in a liquid solution at a moderate temperature (37 °C). The conjugation was verified by UV–Vis spectrometry and electrophoresis analysis. The results suggested that glycation affected the particle size and morphology of MP, and glycation induced unfolding of the MP and loss of α-helix structures. As the molecular weight of DX was increased, the glycated MP displayed shear-thinning behavior with better flow ability and higher solubility, and the solubility at isoelectric point was noticeably improved (P < 0.05). The thermal gelling ability seemed to be impaired, probably because glycation exerted a protective effect on MP by inhibiting aggregation during heat-induced gelation. The results provide a further understanding of the relationship between the structure and functionalities of glycated MP, which can be utilized as a new additive.

Study on the protection of dextran on erythrocytes during drug loading

In comparison to other carriers, erythrocytes (red blood cells, RBCs) hold the advantages of unmatched long circulation, biocompatibility and biodegradability. However, because of the defects in RBCs carriers caused by the drug loading process, the biological activities of drug-loaded RBCs are worse than those of natural RBCs (NRBCs). We aim to study the protective effect of dextran on the activity of drug-loaded RBCs. Different molecular weights of dextran were selected and added to a hypotonic drug solution to prepare drug-loaded RBCs by the hypotonic preswelling method. Water-soluble betamethasone sodium phosphate (BSP) and fat-soluble artesunate (AS) were selected as model drugs. The results showed that the addition of dextran with a molecular weight of 40 kDa and a concentration of 10 % could significantly increase the Na+/K+-ATPase activity, improve the drug loading amount and lower the phosphatidylserine eversion rate. Moreover, it maintained a similar osmotic fragility to NRBCs and exhibited no effect on the morphological structure of drug-loaded RBCs. Laser confocal results showed tight covering of dextran over RBCs, which could explain the protective effects. The addition of dextran increased the activity of drug-loaded RBCs without affecting their in vivo circulation (at least nine days). In conclusion, 10 % dextran with a weight of 40 kDa displayed a significant protective effect on the bioactivity of drug-loaded RBCs, which could be expected to be a better way to facilitate hydrophobic and hydrophilic drug loading by RBCs.

Polymer microspheres for replacement of biological carriers in test systems operating on the principle of latex agglutination reaction

The results of the study of various modification methods of polymer microspheres for their use in immunochemical reactions as bioligand carriers are reported. Ion etching and electron microscopy were used to show that the copolymer microspheres have a porous structure non-uniform in density. The Maillard reaction was used for the first time in the modification of copolymer microspheres by dextrans of different molecular weight as a simplest way of covalent immobilization of saccharides on their surface. The physicochemical properties of polystyrene-divinylbenzene and polyglycidyl methacrylate-ethylene glycol dimethacrylate microspheres modified with diamines and dextrans were determined for the first time. The conditions under which the bioligand (diphtheria toxoid) immobilized on their surface retained the native conformation and the diagnostics obtained on their basis have high sensitivity were revealed.

Cryopreservation of turkey spermatozoa without permeant cryoprotectants

In avian species, cryopreservation of semen is necessary for developing sperm cryobanks. It is very difficult, however to cryopreserve turkey sperm and have sperm be viable after thawing. Glycerol, the commonly used sperm cryoprotectant in many species, is toxic to sperm of avian species. The aim of this study was to evaluate whether the non-permeating dextran was effective for the cryopreservation and maintenance of turkey spermatozoa viability after thawing, avoiding the use of permeating cryoprotectants. Turkey sperm were diluted with a medium supplemented with 11% glycerol or dextran with a 1,000 molecular weight (MW), dextran with a 10,000 MW, or dextran with a 20,000 MW each at a 2%, 5%, or 10% concentration. Sperm kinetic characteristics, membrane and acrosome integrity (AI), and the capacity of spermatozoa to interact with the autologous perivitelline layer were evaluated after equilibration and cryopreservation. Results indicate that with use of glycerol and the 1,000 MW dextran there was lesser sperm viability after both equilibration and cryopreservation, compared with use of the 10,000 or 20,000 MW dextran compounds. There was a greater cryoprotective effect with the 10,000 and 20,000 MW dextran compounds at the 10% concentration with spermatozoa maintaining a greater functionality and capacity to interact with the autologous perivitelline layer. In conclusion, the results of this study indicate turkey spermatozoa could be effectively cryopreserved in extender without the use of glycerol as a penetrating cryoprotectant but with the use of the 10,000 or 20,000 MW dextran compounds at a 10% extender concentration.

Glycation-induced structural modification of myofibrillar protein and its relation to emulsifying properties

In the present study, myofibrillar protein (MP) and dextran (DX) conjugates were prepared via glycation in a liquid solution. The effects of DX molecular weight on structural and emulsifying properties of conjugates compared with those of MP were investigated. The glycation was confirmed by evaluating modification degree of glycation (DG), electrophoresis and Fourier transform infrared spectroscopy. As DX molecular weight increased, the Ca2+-ATPase activity decreased markedly due to modification of MP, and the formation of MP-DX conjugates reduced surface hydrophobicity owing to the unfolding behaviour of MP and covalent attachment of DX. In addition, combined analysis of turbidity and reactive sulfhydryl contents indicated that MP may undergo a conformation unfolding and become looser and more flexible upon glycation. Glycation was able to increase the emulsifying activity and emulsion stability of MP, and MP-DX 70 showed the best emulsifying properties. A good correlation between reactive sulfhydryl contents and emulsifying properties was obtained, and the correlation coefficients were 0.930 for emulsifying activity and 0.961 for emulsion stability. Meanwhile, there was a negative correlation between surface hydrophobicity and emulsifying properties with correlation coefficients of −0.965 and −0.895, respectively. Overall, glycation could alter the structural characteristics and enhance the emulsifying properties of MP.

A Detailed Study on the Fabrication of Surface Plasmon Sensor Chips: Optimization of Dextran Molecular Weight

The present work discusses a detailed study of the fabrication steps of carboxymethyl-dextran SPR sensor chips with specal focus on the effect of dextran molecular weight (40, 200, and 500 kDa) both on the chip physical characteristics after each fabrication step and on toxin detection performance. Physical characterization was performed using ATR-FTIR, AFM, profilometry, and surface plasmon resonance (SPR) as analytical methods. Based on ATR-FTIR spectroscopy analysis, it is demonstrated that NaOH concentration plays a critical role in the epichlorohydrin (ECH) activation step for subsequent dextran molecules covalent bonding and should be less than 0.4 M, preferably 0.2 M. This is in contrast to the concentration of 0.4 M used in conventional protocols. After covalent binding of the monoclonal anti-staphylococcal enterotoxin B (anti-SEB) to the carboxyl groups of dextran matrix, the detection of enterotoxin B as a function of dextran molecular weight has been assessed. Dextran with a molecular weight of 200 kDa results in a distinct larger SPR angle shift of the final chip with respect to 40 and 500 kDa molecular weights. This observation is explained based on the SPR theory and the physico-chemical characteristics of the antibody/dextran layers measured throughout this study. The SPR sensor chip with the dextran molecular weight of 200 kDa may be considered as an appropriate candidate for the detection of proteins with the same molecular weight as enterotoxin B.

Influence of Maillard reaction extent on acid induced gels of whey proteins and dextrans

Maillard reaction is a natural occurring reaction that takes place when proteins and saccharides are present. In this study, we have investigated the effect of Maillard reaction on some physicochemical properties of conjugates of whey proteins isolate (WPI) and dextrans (DX) of different molecular weight and their effects on the mechanical and microstructural properties of acid induced gels. The results indicated that the extent of Maillard reaction depended on DX concentration and DX molecular weight (MW). The higher the DX concentration and the lower the DX MW, the higher the extent of Maillard reaction. Conjugates with DX 6 kDa exhibited a decreased from 4.8 up to 4.4 in the isoelectric point, and a decreased in free sulfhydryl groups from 24.37 to 14.81 μmol SH/gprotein. In order to carried out the acid induced gel formation, all the systems were heated at 9% w/w (68.5 °C for 2 h) to form aggregates, which were confirmed by the increase in intrinsic viscosity values in all the systems. The acid gel formation was carried out by using glucono delta-lactone (GDL), which decreased the pH until the isoelectric point of the systems. WPI/DX conjugates of DX 40 kDa formed acid gels in most all DX concentrations, but the conjugation decreased the gel strength and the Young's modulus as compared with WPI gels. Gelation could not be carried out in systems with DX 6 kDa, indicating that Maillard reaction could change or even inhibit the acid gel formation, depending of its extent. After heating, all the systems increased the surface hydrophobicity (H0) as expected, except for WPI/DX6, which showed similar H0 values before and after heating, indicating that this might be the main reason for the inhibition of gel formation.

Dextran coated superparamagnetic iron oxide nanoparticles produced by microfluidic process

Abstract Dextran coated biocompatible water-based magnetite (Fe3O4) nanostructured media was produced via microfluidic process at various flow rates. The influences of dextran molecular weight on the magnetite particle size and magnetic property of nano fluid were investigated. Magnetite produced at flow rate of 0.04 mL/s showed uniform particle size distribution with average size 10 nm and saturation magnetization (Ms) up to 60 emu/g. The X-ray diffraction pattern indicates pure phase of Fe3O4 as-synthesized nanoparticles with high crystallinity. Zero Field Cooled and Field Cooled measurements indicated a superparamagnetic nature of as synthesized particles with a low blocking temperature that varies by the amount of dextran introduced in the mixture. The Specific Power Absorption (SPA) value obtained of up to 130 W/g shows that the magnetite–dextran nanostructured fluid appears to be a promising active media for the local magnetic hyperthermia for cancer therapy.

Characterization of a dextran-budesonide prodrug for inhalation therapy

Reducing the dosing frequency of corticosteroids may increase compliance and increase pulmonary targeting. The objective of this study was to evaluate whether a high molecular weight dextran-budesonide conjugate might be suitable for pulmonary slow release of the otherwise fast absorbed budesonide. An array of dextran-spacer-budesonide conjugates was prepared that differed in the molecular weight of dextran (20 kDa or 40 kDa) and the length of the dicarboxylic spacer (succinic, glutaric, and adipic anhydride). The conjugates were characterized for identity by proton nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FTIR), the degree of dextran-hydroxyl conjugation, purity, and physiological activation (release of budesonide). The 40 kDa dextran-succinate-budesonide conjugate was formulated as a dry powder for pulmonary delivery and characterized for particle size distribution, particle morphology, and aerodynamic particle size. The degree of substitution (grams of budesonide in 100 g of conjugate) ranged from 4 to 10% for all six dextran-spacer-budesonide conjugates. Incubation at 37 °C and pH 7.4 in phosphate buffered saline resulted in release of 25–75% of the conjugated budesonide over an 8-hour period with the rate of release increasing with molecular weight of dextran and the length of the spacer. Modeling of the concentration time profiles of the released budesonide and budesonide-21-hemisucinate in phosphate buffered saline, suggested that budesonide is generated either directly or via the budesonide-21-hemisucinate pre-cursor. Data also suggested that the rate of budesonide generation likely depends on the position of budesonide on the dextran molecule. Spray-drying the 40 kDa dextran-succinate-budesonide produced respirable particles of the conjugate with a mass median aerodynamic particle size (MMAD) of 4 μm. The slow generation of budesonide from the chemical delivery system might further improve the pharmacological profile of budesonide.

Comparison of dextran molecular weight on wheat bread quality and their performance in dough rheology and starch retrogradation

The aim of this study was to compare effects of linear dextrans (backbones of α-(1 → 6) linkages) varying with weight-average molecular weights (Mw: T10, T70, T250, T750, T2000) on the quality of wheat breads. The firmness of fresh bread crumb was decreased with increasing dextran Mw and the highest Mw dextran (T2000) lowered the staling rate of stored breads. Dough rheology clarified that only the specific dextran (T70) apparently changed dough viscoelastic, strengthening the viscous behavior. Significant decreases in breakdown and setback viscosity of starch slurry were observed by addition of dextrans, especially dextran T2000. Analyses in the long-term retrogradation of starch and starch-gluten systems indicated that the promising antistaling influence of dextran T2000 was caused by either inhibitions of amylopectin retrogradation or beneficial variations induced by gluten. Positive effects of starch-gluten and dextran-gluten associations on amylopectin retrogradation were revealed. These results suggested that the highest Mw dextran (T2000) possessed the potential for increasing consumer acceptance of bread products.

Acoustical and Physical Characteristic of a New Blood Mimicking Fluid Phantom

Offer a blood-mimicking fluids (BMF) for test object of medical ultrasound diagnostic instruments in this article is done. Both the acoustical (speed of sound and attenuation) and physical (density and viscosity) properties were defined and specified in the International Electrotechnical Commission standard and are given as a constant value. However, the viscosity of human blood depends greatly on the shear rate of the blood. In accurate studies that use a specified flow phantom, the BMFs with the appropriate viscosity are required. Furthermore, since the BMF considered as Newtonian, the viscosity it can has an arbitrary viscosity (more than 4.1 mPa.s). This article displays a general overview about the effect of density and molecular weight of dextran which is a component of mixture fluid that was used in BMF preparation. For this reason, we replaced the dextran 185000D (0.90 g/ml) with dextran 150000D powder material (0.25 g/ml). To produce liquids with proper viscosity in unit of mPa.s, we have prepared a new ternary fluid made of water, glycerol and dextran 150000D powder material.

Dopant‐Free Hydrogels with Intrinsic Photoluminescence and Biodegradable Properties

AbstractPhotoluminescent hydrogels that function as both injectable scaffolds and fluorescent imaging probes hold great potential for therapeutics delivery and tissue engineering. Current fluorescent hydrogels are fabricated by either conjugating or doping a fluorescent dye, fluorescent protein, lanthanide chelate, or quantum dot into polymeric hydrogel matrix. Their biomedical applications are severely limited due to drawbacks such as photostability, carcinogenesis, and toxicity associated with the above‐mentioned dopants. Here, a successful development of dopant‐free photoluminescent hydrogels in situ formed by crosslinking of biocompatible polymer precursors is reported, which can be synthesized by incorporating an amino acid to a citric acid based polyester oligomer followed by functionalization of multivalent crosslinking group through a convenient transesterification reaction using Candida Antarctica Lipase B as a catalyst. It is demonstrated that the newly developed hydrogels possess tunable degradation, intrinsic photoluminescence, mechanical properties, and exhibit sustained release of various molecular weight dextrans. In vivo study shows that the hydrogels formed in situ following subcutaneous injection exhibit excellent biocompatibility and emit strong fluorescence under visible light excitation without the need of using any traditional organic dyes. Their in vivo degradation profiles are then depicted by noninvasively monitoring fluorescence intensity of the injected hydrogel implants.

Size and molecular weight determination of polysaccharides by means of nano electrospray gas-phase electrophoretic mobility molecular analysis (nES GEMMA).

Size, size distribution and molecular weight (MW) determination of nanoparticles and that are for example large polymers, are of great interest and pose an analytical challenge. In this context, nano electrospray gas‐phase electrophoretic mobility molecular analysis (nES GEMMA) is a valuable tool with growing impact. Separation of single‐charged analytes according to their electrophoretic mobility diameter (EMD) starting from single‐digit EMDs up to several hundred nm diameters is possible. In case of spherical analytes, the EMD corresponds to the dry nanoparticle size. Additionally, the instrument is capable of number‐based, single‐particle detection following the recommendation of the European Commission for nanoparticle characterization (2011/696/EU). In case an EMD/MW correlation for a particular compound class (based on availability of well‐defined standards) exists, a nanoparticle's MW can be determined from its EMD. In the present study, we focused on nES GEMMA of linear and branched, water‐soluble polysaccharides forming nanoparticles and were able to obtain spectra for both analyte classes regarding single‐charged species. Based on EMDs for corresponding analytes, an excellent EMD/MW correlation could be obtained in case of the branched natural polymer (dextran). This enables the determination of dextran MWs from nES GEMMA spectra despite high analyte polydispersity and in a size/MW range, where classical mass spectrometry is limited. EMD/MW correlations based on linear (pullulans, oat‐ß‐glucans) polymers were significantly different, possibly indicating challenges in the exact MW determination of these compounds by, for example, chromatographic and light scattering means. Despite these observations, nES GEMMA of linear, monosaccharide‐based polymers enabled the determination of size and size‐distribution of such dry bionanoparticles.

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.