scholarly journals Dextran Sulfate/Pramlintide Polyelectrolyte Nanoparticles as a Promising Delivery System: Optimization, Evaluation of Supramolecular Interactions and Effect on Conformational Stability of the Peptide Drug

2021 ◽  
Author(s):  
Carine Zuglianello ◽  
Andrés Chamorro ◽  
Vanessa de Oliveira ◽  
Francisco Xavier Jr. ◽  
Elenara Lemos-Senna
Keyword(s):  
Colloidal Stability ◽  
Dextran Sulfate ◽  
Conformational Stability ◽  
System Optimization ◽  
Physicochemical Characteristics ◽  
Supramolecular Interactions ◽  
New Approach ◽  
Isothermal Titration Microcalorimetry ◽  
Peptide Release ◽  
Helical Content

In this study, we investigated the feasibility to obtain nanoparticles (NPs) by assembling pramlintide (Pram) with dextran sulfate (DexS), as a new approach for mucosal peptide delivery. DexS/Pram NPs were prepared by dropwise addition of a Pram solution to a DexS solution under magnetic stirring. The physicochemical characteristics of NPs and molecular interactions involved in the co-assembling were evaluated by dynamic light scattering (DLS), transmission electronic microscopy (TEM), isothermal titration microcalorimetry, Fourier-transform infrared spectroscopy (FTIR), fluorescence quenching, and circular dichroism (CD). DexS/Pram NPs displayed a narrow size distribution (ca. 200 nm), negative zeta potential (ca. −40 mV), association efficiency close to 100%, and nanogel behavior. The assembling with DexS increased the Pram α-helical content, stabilizing the peptide in its bioactive form. The colloidal stability of nanoparticles was dependent on the salt concentration and it could be assumed that peptide release from nanoparticles occurs by dissociation of the complex at physiological conditions.

scholarly journals The Effect of pH and Viscosity on Magnetophoretic Separation of Iron Oxide Nanoparticles

2021 ◽  
Vol 7 (6) ◽  
pp. 80
Author(s):  
Leonie Wittmann ◽  
Chiara Turrina ◽  
Sebastian P. Schwaminger
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Colloidal Stability ◽  
Downstream Processing ◽  
Physicochemical Characteristics ◽  
Particle Migration ◽  
Aggregation Behavior ◽  
Oxide Nanoparticles ◽  
Separation Processes ◽  
Effect Of Ph

Magnetic nanoparticles (MNPs) are used for magnetophoresis-based separation processes in various biomedical and engineering applications. Essential requirements are the colloidal stability of the MNPs and the ability to be separated even in low magnetic field gradients. Bare iron oxide nanoparticles (BIONs) with a diameter of 9.2 nm are synthesized via coprecipitation, exhibiting a high saturation magnetization of 70.84 Am2 kg−1 and no remanence. In our study, zeta potential, dynamic light scattering (DLS), and sedimentation analysis show that the aggregation behavior of BIONs is influenced by pH and viscosity. Small aggregate clusters are formed with either low or high pH values or increased viscosity. Regarding magnetophoresis-based separation, a higher viscosity leads to lower magnetophoretic velocities, similar to how small aggregates do. Additionally, cooperative magnetophoresis, the joint motion of strongly interacting particles, affects the separation of the BIONs, too. Our study emphasizes the effect of pH and viscosity on the physicochemical characteristics of MNPs, resulting in different aggregation behavior. Particularly, for high viscous working media in downstream processing and medicine, respectively, the viscosity should be taken into account, as it will affect particle migration.

scholarly journals ATP and Tri-Polyphosphate (TPP) Suppress Protein Aggregate Growth by a Supercharging Mechanism

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1646
Author(s):  
Jordan Bye ◽  
Kiah Murray ◽  
Robin Curtis
Keyword(s):  
Protein Interactions ◽  
Electrostatic Interactions ◽  
Colloidal Stability ◽  
Conformational Stability ◽  
Kinetic Studies ◽  
Structural Factors ◽  
Protein Protein Interactions ◽  
Protein Aggregate ◽  
Aggregate Growth

A common strategy to increase aggregation resistance is through rational mutagenesis to supercharge proteins, which leads to high colloidal stability, but often has the undesirable effect of lowering conformational stability. We show this trade-off can be overcome by using small multivalent polyphosphate ions, adenosine triphosphate (ATP) and tripolyphosphate (TPP) as excipients. These ions are equally effective at suppressing aggregation of ovalbumin and bovine serum albumin (BSA) upon thermal stress as monitored by dynamic and static light scattering. Monomer loss kinetic studies, combined with measurements of native state protein–protein interactions and ζ-potentials, indicate the ions reduce aggregate growth by increasing the protein colloidal stability through binding and overcharging the protein. Out of three additional proteins studied, ribonuclease A (RNaseA), α-chymotrypsinogen (α-Cgn), and lysozyme, we only observed a reduction in aggregate growth for RNaseA, although overcharging by the poly-phosphate ions still occurs for lysozyme and α-Cgn. Because the salts do not alter protein conformational stability, using them as excipients could be a promising strategy for stabilizing biopharmaceuticals once the protein structural factors that determine whether multivalent ion binding will increase colloidal stability are better elucidated. Our findings also have biological implications. Recently, it has been proposed that ATP also plays an important role in maintaining intracellular biological condensates and preventing protein aggregation in densely packed cellular environments. We expect electrostatic interactions are a significant factor in determining the stabilizing ability of ATP towards maintaining proteins in non-dispersed states in vivo.

scholarly journals Factor XII-independent activation of factor XI in plasma: effects of sulfatides on tissue factor-induced coagulation

Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 813-819 ◽  
Author(s):  
D Gailani ◽  
GJ Jr Broze
Keyword(s):  
Tissue Factor ◽  
Gel Electrophoresis ◽  
Dextran Sulfate ◽  
Polyacrylamide Gel Electrophoresis ◽  
Factor Xii ◽  
Factor Xi ◽  
Enhancing Effect ◽  
Peptide Release ◽  
Plasma Effects ◽  
Release Assay

Abstract Factor XI (FXI) may be activated in a purified system by thrombin and by autoactivation in the presence of negatively charged substances such as dextran sulfate or sulfatides. The current studies were performed to determine if these processes occur during the coagulation of plasma. FXII--deficient plasma was supplemented with 125I-FXI and clot formation was induced with tissue factor and/or sulfatides. Cleavage of FXI was studied by standard polyacrylamide gel electrophoresis and autoradiography. Activated FXI (FXIa) was detected after 20 minutes of incubation with sulfatides alone and this process was markedly accelerated by the addition of tissue factor (TF). The enhancing effect of TF was blocked by hirudin, which indicated thrombin involvement in FXI activation. The contribution of FXIa to FIX activation in this system was studied using a 3H-FIX activation peptide release assay. Sulfatides increased FIX activation about twofold in plasma induced to clot with TF but had no effect if the plasma was immunodepleted of FXI. FIX activation was also increased in plasma induced to clot with FXa if sulfatides were present. The enhanced generation of FIXa was dependent on FXI and was blocked by hirudin. Some activation was seen in the reactions with sulfatides and hirudin and is likely solely caused by FXI autoactivation. The data indicate that during the coagulation of plasma in the presence of sulfatides, FXI is activated by a mechanism that is thrombin dependent and does not require FXII.

A New Approach on Mounting Systems Optimization

2003 ◽  
Author(s):  
Reza Madjlesi ◽  
Amir Khajepour ◽  
Brad Schubert ◽  
Fathy Ismail
Keyword(s):  
Path Analysis ◽  
Optimization Technique ◽  
Optimization Procedure ◽  
System Optimization ◽  
Optimization Method ◽  
Trial And Error ◽  
Target Response ◽  
New Approach ◽  
Weakly Coupled ◽  
Noise Vibration

Vehicles are assemblies of subsystems or modules, which are developed in parallel at multiple locations and often for more than one vehicle. CAE software provides the integration of modules in a complete vehicle in parallel; however the whole system requires final adjustments and tunings. These adjustments, especially in suspensions and mounting systems are very time consuming and are generally based upon trial and error techniques. To reduce the number of trials, usually noise path analysis (NPA) is used. In this technique, the noise and vibration paths for each mount to the objective point are measured. Using the measured data, the dominant path is detected. A highly experienced NVH engineer now can use the information to tune the mount to satisfy the target response. This technique is appropriate if the subsystems are weakly coupled. This situation is not usually the case in engine mounting systems where any modification in one of the mounts may change the dominant path. An important step to reduce refinement time is to develop a method to obtain the overall model of the whole vehicle. In this paper, we introduce a new approach in vehicle’s NVH development. In this approach, the model of the vehicle for mounting system optimization is obtained based on the FRF synthesis. A hybrid analytical/experimental model of the vehicle is developed to predict the NVH response of the vehicle for any given mounting system. This model along with an optimization technique is used to arrive at the optimum mounting system for any objective function. The optimization method is linked with the noise path analysis (NPA), which is used to specify the dominant directions that the noise/vibration is transferred to the response point. These directions are used in the optimization procedure to find the optimum mounting system with minimum calculation time. Experimental results on a full size car are presented to evaluate new approach.

scholarly journals Effect of Plant Extracts on the Characteristics of Silver Nanoparticles for Topical Application

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1244
Author(s):  
Ioanna K. Siakavella ◽  
Fotini Lamari ◽  
Dimitrios Papoulis ◽  
Malvina Orkoula ◽  
Patroula Gkolfi ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Colloidal Stability ◽  
Skin Barrier ◽  
Physicochemical Characteristics ◽  
Total Phenolic ◽  
Flavonoid Content ◽  
Laser Scattering ◽  
The Impact ◽  
Phenolic And Flavonoid

Silver nanoparticles (AgNPs) were synthesized using hydroalcoholic extracts of dittany (Origanum dictamnus), sage (Salvia officinalis), sea buckthorn (Elaeagnus rhamnoides, syn. Hippophae rhamnoides), and calendula (Calendula officinalis) as reducing agents. AgNPs synthesized using NaBH4 and citric acid were used as control. The impact of the origin of the extract and preparation conditions (light, temperature, reaction time) on the properties of the synthesized AgNPs was investigated. The structure, morphology, composition, physicochemical characteristics, and colloidal stability were characterized using dynamic laser scattering (DLS), ultraviolet-visible spectrophotometry (UV–/Vis), XRD, X-ray fluorescence (XRF), TEM, and FTΙR. The reduction of total phenolic and flavonoid content of the extracts after the reaction of AgNPs synthesis was also determined. Low IC50 values for all types of AgNPs revealed good antioxidant activity, attributable to the phenolic and flavonoid content of their surface. The results suggest that plant extract selection is important to the green synthesis of AgNPs because it affects the kinetics of their synthesis as well as their morphology, physicochemical characteristics, and colloidal stability. In vitro permeation studies on porcine skin revealed that AgNPs remained at the upper layers of stratum corneum and did not penetrate the skin barrier after 4 h of cutaneous application suggesting the safety of their application on intact skin for a relatively short time.

Physical Stability of Albinterferon-α2b in Aqueous Solution: Effects of Conformational Stability and Colloidal Stability on Aggregation

2012 ◽  
Vol 101 (8) ◽  
pp. 2702-2719 ◽  
Author(s):  
Danny K. Chou ◽  
Rajesh Krishnamurthy ◽  
Mark Cornell Manning ◽  
Theodore W. Randolph ◽  
John F. Carpenter
Keyword(s):  
Aqueous Solution ◽  
Colloidal Stability ◽  
Conformational Stability ◽  
Physical Stability

Biomedical Engineered Ferrofluids

2007 ◽  
Vol 1032 ◽  
Author(s):  
Birgit Fischer ◽  
Leidong Mao ◽  
Mustafa Gungormus ◽  
Candan Tamerler-Behar ◽  
Mehmet Sarikaya ◽  
...  
Keyword(s):  
Colloidal Stability ◽  
Ac Susceptibility ◽  
Medical Application ◽  
Genetically Engineered ◽  
Monodisperse Particles ◽  
New Approach ◽  
Water Based ◽  
Liquid Behavior ◽  
Efficient Route ◽  
The Stability

AbstractThe characteristic of combining liquid behavior with and magnetic properties makes ferrofluids unique and it provides them a variety of applications, in particular in the medial field. For medical application ferrofluids are required to be stable at neutral pH and against high salt concentration. Here we present a new approach to stabilize water-based ferrofluids by using genetically engineered peptides for inorganics (GEPI's). Such GEPI's selected for specific and strong binding to the surface of nanoparticles not only increase colloidal stability by acting as a thin surfactant, but they also enable an efficient route for rendering the ferrofluid bio-functional and bio-compatible. The stability of a ferrofluid was characterized by the ac-susceptibility and by using it in a ferro-microfluidic device. This chip actuates the ferrofluid directly via magnetic fields alone, and the pumping spectrum as a function of frequency reveals information about the size of the magnetic nanoparticles. An ideal ferrofluid with monodisperse particles displays a single and clear pumping peak. Agglomeration can directly be observed as a broadening of the pumping spectrum.

scholarly journals Physics-Based and Data-Enhanced Model for Electric Drive Sizing during System Design of Electrified Powertrains

Vehicles ◽  
2021 ◽  
Vol 3 (3) ◽  
pp. 512-532
Author(s):  
Lukas Decker ◽  
Daniel Förster ◽  
Frank Gauterin ◽  
Martin Doppelbauer
Keyword(s):  
Electric Drive ◽  
System Optimization ◽  
Parameter Variation ◽  
New Approach ◽  
Component Sizing ◽  
Electric Drive System ◽  
Powertrain System ◽  
Proposed Model ◽  
Feasible Range ◽  
Drive Systems

In multi-drive electrified powertrains, the control strategy strongly influences the component load collectives. Due to this interdependency, the component sizing becomes a difficult task. This paper comprehensively analyses different electric drive system sizing methods for multi-drive systems in the literature. Based on this analysis, a new data-enhanced sizing approach is proposed. While the characteristic is depicted with a physics-based polynomial model, a data-enhanced limiting function ensures the parameter variation stays within a physically feasible range. Its beneficial value is demonstrated by applying the new model to a powertrain system optimization. The new approach enables a detailed investigation of the correlations between the characteristic of electric drive systems and the overall vehicle energy consumption for varying topologies. The application results demonstrate the accuracy and benefit of the proposed model.

Sign in / Sign up

Export Citation Format

Share Document