•New amines(aq) solutions densities and isobaric heat capacities experimental data over a wide range of conditions.•Density and isobaric heat capacity decrease with amine mass fraction.•A modified ...Tammann-Tait Equation represents experimental density as a function of temperature, pressure, and molality.•Experimental data agrees with reported literature data within uncertainties.•Isobaric heat capacity is well-represented with an empirical correlation as a function of temperature and composition.
Densities and isobaric heat capacities of DEAE + H2O and EAE + H2O systems are presented in this paper. Density measurements were carried out at high pressure (up to 100 MPa) and temperatures from (293.15 to 393.15) K, with amine mass fractions of 0.1; 0.2; 0.3 and 0.4. These data were gathered using a vibrating tube densimeter (Anton Paar DMA HPM) with a relative expanded uncertainty of ±0.1 % (k = 2). A non-adiabatic quasi-isothermal flow calorimeter was used for isobaric heat capacity measurements with a relative expanded uncertainty better than 1 % (k = 2). Measurements reached pressures up to 25 MPa, and temperatures from (293.15 to 353.15) K, with amine mass fractions of 0.1; 0.2; 0.3 and 0.4. Both amine DEAE + H2O and EAE + H2O systems show a density and isobaric heat capacity decrease with amine mass fraction increase. Density data as a function of temperature, pressure and molality were fitted using a modified Tammann-Tait empirical equation of state. Furthermore, isobaric heat capacity data were correlated using an empirical function of temperature and amine mass fraction, but not pressure due to its lack of sensitivity in the measured data. Both correlations are in good agreement with the uncertainties. Comparison with experimental density data available in literature showed lower deviations than the associated uncertainties. Our isobaric heat capacity experimental data agree well with the scarce literature.
mRNA pharmaceuticals represent a new class of therapeutics, with applications, in cancer vaccination, tumour therapy and protein substitution. Formulations are required to deliver messenger RNA ...(mRNA) to the target sites where induction of genetic transfection following receptor mediated cell uptake & translation is required.
In the current study, the cationic polysaccharide diethylaminoethylen (DEAE) – Dextran was selected as a model system carrier for the investigation of polyplex nanoparticle formation together with mRNA as a function of the molar ratio of the components. The structure of the mRNA/Dextran colloids was investigated as a function of the polymer-to-mRNA ratio and correlated with the biological activity determined by cellular transfection with luciferase coding mRNA. Dynamic light scattering (DLS), small angle x-ray scattering (SAXS), and small angle neutron scattering (SANS) with deuterium contrast variation were used to achieve structural insight into the systems. Similarly to previously investigated lipid based systems, colloidally stable particles with confined size were obtained with either excess of positive or negative charge. Highest activity was obtained with positive charge excess. From the scattering experiments information on the internal organization inside the polymer/mRNA systems was derived. Indication for the presence of structural elements in the length scale of ten to 20 nm were found in the excess of dextran, which could be due to either excess or particulate polymer. Information on the molecular organization of the mRNA nanoparticle products may provide a valuable basis for defining critical quality attributes of drug products for pharmaceutical application.
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In participants with pulmonary arterial hypertension, 24 weeks of sotatercept resulted in a significantly greater reduction from baseline in pulmonary vascular resistance than placebo. This report ...characterises the longer-term safety and efficacy of sotatercept in the PULSAR open-label extension. We report cumulative safety, and efficacy at months 18-24, for all participants treated with sotatercept.
PULSAR was a phase 2, randomised, double-blind, placebo-controlled study followed by an open-label extension, which evaluated sotatercept on top of background pulmonary arterial hypertension therapy in adults. Participants originally randomised to placebo were re-randomised 1:1 to sotatercept 0.3 or 0.7 mg·kg
(placebo-crossed group); those initially randomised to sotatercept continued the same sotatercept dose (continued-sotatercept group). Safety was evaluated in all participants who received ≥1 dose of sotatercept. The primary efficacy endpoint was change from baseline to months 18-24 in pulmonary vascular resistance. Secondary endpoints included 6-min walk distance and functional class. Two prespecified analyses, placebo-crossed and delayed-start, evaluated efficacy irrespective of dose.
Of 106 participants enrolled in the PULSAR study, 97 continued into the extension period. Serious treatment-emergent adverse events were reported in 32 (30.8%) participants; 10 (9.6%) reported treatment-emergent adverse events leading to study discontinuation. Three (2.9%) participants died, none considered related to study drug. The placebo-crossed group demonstrated significant improvement across primary and secondary endpoints and clinical efficacy was maintained in the continued-sotatercept group.
These results support the longer-term safety and durability of clinical benefit of sotatercept for pulmonary arterial hypertension.
Ion-Exchange Chromatography (IEC) allows for the separation of ionizable molecules on the basis of differences in charge properties. Its large sample-handling capacity, broad applicability ...(particularly to proteins and enzymes), moderate cost, powerful resolving ability, and ease of scale-up and automation have led to it becoming one of the most versatile and widely used of all liquid chromatography (LC) techniques. In this chapter, we review the basic principles of IEC, as well as the broader criteria for selecting IEC conditions. By way of further illustration, we outline basic laboratory protocols to partially purify a soluble serine peptidase from bovine whole brain tissue, covering crude tissue extract preparation through to partial purification of the target enzyme using anion-exchange chromatography. Protocols for assaying total protein and enzyme activity in both pre- and post-IEC fractions are also described.
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•DEAE cellulose was used as adsorbent for coliphages, MS2 and SUSP2.•Moringa oleifera seed protein functionalized rice husk ash (FaRHA) was also used.•DEAE cellulose had relatively ...higher adsorption capacity for the coliphages.•DEAE cellulose could be regenerated and reused using the optimized eluents.•Rotavirus could also be effectively adsorbed and desorbed from DEAE cellulose.
Adsorption elution technique is widely used for virus preconcentration before detection and quantification. However, the existing methods do not provide adequate recovery of viruses. DEAE cellulose, and Moringa oleifera seed protein functionalized rice husk ash (FaRHA) adsorbents were evaluated for the concentration of an enteric virus, Rotavirus A (RVA), an F-specific coliphage, MS2, and a somatic coliphage, SUSP2. Recovery with various adsorbent-eluent pairs was tested using initial coliphage concentration (Co) 104 PFU/mL. An eluent composed of 1.5 M NaCl, 2% Tween 80, and 0.05 M KH2PO4 (pH 9.2) yielded a high recovery of MS2 from DEAE cellulose (82%) and it also yielded high recovery of RVA. However, SUSP2 recovery from DEAE cellulose was ~61%, even after eluent optimization. An eluent comprised of glycine 3X broth, 1.5 M NaCl, 3% Tween 80, and 0.05 M KH2PO4 (pH 10.2) yielded high recovery of SUSP2 from FaRHA (88%). The maximum recovery of MS2 and RVA from FaRHA was lower (77% and 32%, respectively). The Freundlich model provided a good fit to the adsorption-desorption isotherms for the coliphages. For both the coliphages, the Freundlich capacity parameter, KF, was two orders of magnitude higher for DEAE cellulose compared to FaRHA. MS2 recovery from DEAE cellulose was minimally affected by antichaotrophic ions and dissolved organic matter, and higher sorption could be achieved over a wide pH range. For FaRHA, pH variation and various water matrices had a significant adverse effect on coliphage recovery. Thus, DEAE cellulose is a superior adsorbent for virus preconcentration from water samples.
► Increasing of −CH2−CH2−N⊕H2−(C2H5)2 groups, network structure expands and increases swelling. ► It was thought that diethylaminoethyl group increases adsorption of metal ions. ► Decreasing order of ...metal removal strength of gel: Mn2+>Zn2+>Pb2+>Cd2+. ► Hydrogel can be used by aim of removing unwanted water or chemical substances.
Epichlorohydrin-crosslinked diethylaminoethyl dextran (DEAE-D/ECH) hydrogel was synthesized by intermolecular side-chain reaction of DEAE-D hydroxyl groups with monomeric crosslinking agent, ECH. Swelling ability, adsorption capacity and metal removal of the hydrogel were profoundly determined and some structural parameters for the hydrogel such as volume of non-swollen gel, percentages of gellation, swelling ratio and equilibrium water content were evaluated in this study.
The ability of removing heavy metal ions from Orontes River by the synthesized hydrogel, thoroughly characterized by photometric spectrometer and the adsorption characteristics of metal ions, was investigated as well as surface morphologies of the hydrogel before and after metal adsorption were examined by SEM.
Structure of DEAE-D/ECH gel was analyzed by FTIR, TGA, and DSC. Gellation point of binary system reaction between DEAE-D and ECH was determined via monitoring viscosity changes during reaction. The order of affinity based on amount of metal ion uptake was found as follows: Zn2+>Mn2+>Pb2+>Cd2+.
Cancer has emerged as a global threat with challenges for safe chemotherapeutics. Most of the currently available anti-cancer drugs exhibit significant toxicity. Amongst novel agents, interferons ...have exhibited anti-proliferative and cytoprotective roles. However, due to stability drawbacks of interferons, we have identified an interferon inducer DEAE-Dextran, which resolves the stability issues. Based on the previous history of toxicity pertaining to the current chemotherapeutic agents, it is equally essential to determine the safety of DEAE-Dextran. In the present study, repeated dose 28 day oral toxicity of DEAE-Dextran has been evaluated in accordance to OECD-407. We found absence of any CNS behavioral changes related to self-mutilation, walking backwards, aggressiveness on handling or tonic-clonic seizures during the 28 day study. Neither the motor activity nor grip strength was altered during the treatment duration with DEAE-Dextran implying absence of any effect on the skeletal muscles. Interestingly, we also found that treatment with DEAE-Dextran did not present any significant cardiac, hepatic, renal, gastrointestinal, lymphatic or reproductive system toxicity or alteration in the body's normal physiology based upon the various organ function tests. Henceforth, it may be concluded that DEAE-Dextran is a safe anti-cancer agent devoid of any sub-acute toxicity.
•Breast cancer treatment faces challenges of safe chemotherapeutic agents since they exhibit toxicity.•Interferon inducers could manifest safe drugs since they enhance the natural defense mechanism of the body.•DEAE-Dextran investigated as an anti-cancer agent, it is adequately important to determine its toxicity profile.•Toxicity profile of DEAE-Dextran indicates no alteration in body system functions declaring it safe for administration.
•Anionic and cationic polyelectrolyte based on polysaccharide complexes are studied.•Zeta potential and ITC measurements show an atypical complexe stoichiometry (0.6).•Deviation from the 1:1 ratio is ...due to inaccessibility of some cationic charges.•PECs aggregates are evidenced by AsF4/MALS/DRI analysis.
The formation of polyelectrolyte complexes (PECs) between carboxymethyl pullulan and DEAE Dextran, was investigated, in dilute solution, with emphasis on the effect of charge density (molar ratio or pH) and molar masses. Electrophoretic mobility measurements have evidenced that insoluble PECs (neutral electrophoretic mobility) occurs for charge ratio between 0.6 (excess of polycation) and 1 (stoichiometry usual value) according to the pH. This atypical result is explained by the inaccessibility of some permanent cationic charge when screened by pH dependant cationic ones (due to the Hoffman alkylation). Isothermal titration calorimetry (ITC) indicates an endothermic formation of PEC with a binding constant around 105Lmol−1. Finally asymmetrical flow field flow fractionation coupled on line with static multi angle light scattering (AF4/MALS) evidences soluble PECs with very large average molar masses and size around 100nm, in agreement with scrambled eggs multi-association between various polyelectrolyte chains.
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