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Absorber layers comprised of shear thickening fluid (STF) intercalated Kevlar ® (STF-Armor TM ) are integrated within the standard extra-vehicular activity (EVA) suit and tested for efficacy against both needle puncture and hypervelocity impact (HVI) tests characteristic of micrometeoroids and orbital debris (MMOD). An improvement in puncture resistance against hypodermic needle threats is achieved by substituting STF-Armor TM in place of neoprene-coated nylon as the absorber layer in the standard EVA suit. The prototype lay-ups containing STF-Armor TM have the benefit of being 17% thinner and 13% lighter than the standard EVA suit and the ballistic limit is identified in HVI testing. The results here demonstrate that EVA suit lay-ups containing STF-Armor TM as absorber layers offer meaningful resistance to MMOD threats. [ABSTRACT FROM AUTHOR]

• The method to study the microstructure of asphalt binders by SANS was established. • The microstructure of asphalt binders was found and the micelle size was calculated. • The relationship between rheological properties and microstructure of asphalt was analyzed. • The SBS modified mechanism was proved by SANS. The microstructure of asphalt binders is believed to have a significant impact on the performance of binders used in roadway constructions. However, there are only limited studies of their nanoscale to microscale structures. Here, small angle neutron scattering (SANS) is used to study the nanoscale structure of neat asphalt binder, styrene-butadienestyrene (SBS) block copolymers and SBS modified asphalt binder. The SANS pattern for asphalt binder demonstrates that it exhibits a colloidal structure comprised of asphaltenes surrounded by resins dispersed in saturates and aromatics. Fractal-core-shell model fits to these patterns indicate that the asphaltene core size decreases with increasing temperature. Both SANS and rheology confirm that SBS modified asphalt has a thermo-reversible phase transition around 110 °C, where the SBS micelles swell and lose scattering contrast above this temperature. The thermo-reversibility of this phenomenon indicates that the mechanism of SBS modification is mostly a physical modification of the nanoscale structure as proposed in the colloidal model of asphalt. Modeling of the SANS patterns shows that neat SBS and SBS dispersed in asphalt binder have a lamellar structure surrounded by a shell. These results are useful for understanding the relationship between the nanoscale structure of asphalt binder and pavement performance, as well as potentially developing new types of modified asphalt binders. [ABSTRACT FROM AUTHOR]

Multi-injection pharmaceutical products such as insulin must be formulated to prevent aggregation and microbial contamination. Small-molecule preservatives and nonionic surfactants such as poloxamer 188 (P188) are thus often employed in protein drug formulations. However, mixtures of preservatives and surfactants can induce aggregation and even phase separation over time, despite the fact that all components are well dissolvable when used alone in aqueous solution. A systematic study is conducted here to understand the phase behavior and morphological causes of aggregation of P188 in the presence of the preservatives phenol and benzyl alcohol, primarily using small-angle x-ray scattering (SAXS). Based on SAXS results, P188 remains as unimers in solution when below a certain phenol concentration. Upon increasing the phenol concentration, a regime of micelle formation is observed due to the interaction between P188 and phenol. Further increasing the phenol concentration causes mixtures to become turbid and phase-separate over time. The effect of benzyl alcohol on the phase behavior is also investigated. [ABSTRACT FROM AUTHOR]

The topology of self-assembled surfactant solutions includes varying degrees of micellar branching, ranging from linear wormlike micelles to a micellar network. Micellar branching acts as an effective attraction between micelles such that network condensation can lead to phase separation. Unlike chemical branching in polymers, micellar branches are labile. Movement of branches along a micelle contour has therefore been proposed as a mechanism of stress relaxation that leads to a reduction in the structural relaxation time and thus, the zero-shear viscosity. Branching is also thought to suppress flow alignment, and for lower levels of branching, may also suppress instabilities such as shear banding. The suppression of shear banding can lead to a lesser degree of shear-thinning in the apparent viscosity at higher shear rates, as well as a reduction in extensional thickening. However, for higher levels of branching, shear can induce branching for samples in proximity to such a phase transition, which can result in shear banding due to shear-induced phase separation. Recent modeling and simulations of the energetics of branching, as well as experiments on model systems, show that the reduction in zero-shear viscosity is due to micelle branching. Current research includes efforts to develop a more mechanistic, quantitative understanding of micellar branching and more generally, its effects on micellar solution rheology. [ABSTRACT FROM AUTHOR]

An extensive data set has been developed and used to further the progress of a model-informed design of controlled drug release. An improved drug-release model with mechanistic modeling of hydrolytic polymer degradation is used and validated by comparing model predictions to in vitro experiments. Combining parameter estimates from the literature with model fits to the data set, this study can aid in achieving a priori design of controlled drug release from a model PLGA release system. A systematic series of model release systems were formulated with FITC-labeled dextran, as a surrogate for biopharmaceuticals, in PLGA rods over a broad range of compositions. While general comparisons between the model and experiments were favorable, important discrepancies were identified for several formulations with significant first-phase drug release. Supported by cross-sectional fluorescence microscopy images of the FITC-dextran distribution within the rods, this first-phase release was attributed to a combination of two main factors: (1) percolation of the drug particles and (2) swelling of and pore formation in the rods due to water uptake. These observations indicate the importance of careful selection of the PLGA polymer grade when designing drug release systems but also reflect a need for better understanding of phenomena such as pore formation. Adapting model parameters, without modifying the physical processes included in the model, enabled accurate fitting of the experimental data for all formulations, highlighting the applicability of the model. [ABSTRACT FROM AUTHOR]

Abstract: Complex fluids with high concentrations of crystallizing fatty acids are important for consumer skin care products. These fluids exhibit solid-like elastic behavior at rest, but yield and flow under an applied strain. Such behavior is characteristic of isotropic, space-filling networks. The processing determines the microstructure of these systems, which in turn influences their macroscopic rheological properties. The kinetics of crystal growth in model system compositions, comprising (by weight) 9% sodium dodecyl sulfate, 3% cocamidopropyl betaine, and different specified amounts of palmitic acid in H2O or D2O, were studied by time domain nuclear magnetic resonance (TDNMR) and differential scanning calorimetry (DSC). The data were analyzed using the Avrami equation; both DSC and TDNMR gave consistent Avrami exponent values of approximately 1.5 for formulations with 11wt% and greater amounts palmitic acid content. The Avrami exponent is consistent with two-dimensional crystal growth limited both by diffusion and surface incorporation. The solids content at 25°C was found to be proportional to the concentration of palmitic acid level above its solubility limit of ca. 2wt%. TDNMR, combined with DSC, microscopy, and rheology provide valuable insights into the molecular structure and mechanism of crystallization in surfactant/fatty acid systems. [Copyright &y& Elsevier]

Abstract: Complex fluids with high concentrations of crystallizing fatty acids are important for consumer care products. The key features of these materials are their ability to support their weight under gravity and to yield or flow beyond a critical applied strain. To better understand the post-processing behavior of these systems, we have utilized a combination of Rheology, Differential Scanning Calorimetry, X-ray scattering, and Polarized Light Microscopy to study a model formulation consisting of two synthetic surfactants and a fatty acid (n-hexadecanoic acid) in water. Homogeneous samples with high storage modulus (G′) are realized due to the formation of a space filling solid fatty acid crystal network. A minimum of 5–7wt% of fatty acid is required to achieve the formation of a percolating crystal network. The storage modulus, yield stress and strain of these formulations show a non-monotonic increase with fatty acid content. This is attributed to the change in the fatty acid crystal habit from large to small aspect ratio plates. We hypothesize that the fatty acid crystal network consists of crystal aggregates linked by surfactant-fatty acid gels, rendering the desired paste-like characteristics to the formulation. The combination of methods utilized in this research provides a framework for understanding crystallizing systems. [Copyright &y& Elsevier]

Abstract: Hydrogel materials are promising vehicles for the delivery of protein therapeutics. Proteins can impart physical interactions, both steric and electrostatic in nature, that influence their release from a given gel network. Here, model proteins of varying hydrodynamic diameter and charge are directly encapsulated and their release studied from electropositive fibrillar hydrogels prepared from the self-assembling peptide, MAX8. Hydrogelation of MAX8 can be triggered in the presence of proteins for their direct encapsulation with neither effect on protein structure nor the hydrogel’s mechanical properties. Bulk release of the encapsulated proteins from the hydrogels was assessed for a month time period at 37 °C before and after syringe delivery of the loaded gels to determine the influence of the protein structure on release. Release of positively charged and neutral proteins was largely governed by the sterics imposed by the network. Conversely, negatively charged proteins interacted strongly with the positively charged fibrillar network, greatly restricting their release to <10% of the initial protein load. Partition and retention studies indicated that electrostatic interactions dictate the amount of protein available for release. Importantly, when protein encapsulated gels were delivered via syringe, the release profiles of the macromolecules show the similar trends as those observed for non-sheared gels. This study demonstrates that proteins can be directly encapsulated in self assembled MAX8 hydrogels, which can then be syringe delivered to a site where subsequent release is controlled by protein structure. [Copyright &y& Elsevier]

Abstract: Self-assembling peptide hydrogels are used to directly encapsulate and controllably release model FITC–dextran macromolecules of varying size and hydrodynamic diameters. MAX1 and MAX8 are two peptide sequences with different charge states that have been designed to intramolecularly fold and self assemble into hydrogels at physiological buffer conditions (pH 7.4, 150mm NaCl). When self-assembly is initiated in the presence of dextran or protein probes, these macromolecules are directly encapsulated in the gel. Self-diffusion studies using fluorescence recovery after photobleaching (FRAP) and bulk release studies indicate that macromolecule mobility within, and release out of, these gels can be modulated by varying the hydrogel mesh size. The average mesh size can be modulated by simply varying the concentration of a given peptide used to construct the gel or by altering the peptide sequence. In addition, results suggest that electrostatic interactions between the macromolecules and the peptide network influence mobility and release. Depending on probe size, release half-lives can be varied from 8h to over a month. [Copyright &y& Elsevier]

Abstract: A microfluidic process for producing crystals of controlled size by confining the crystallization within drops is demonstrated. The process consists of a drop producing stage which segments the mother liquor into monodisperse drops followed by crystallization in a temperature controlled tubular crystallizer. The process is implemented to produce lactose crystals with significantly narrower crystal size distribution (CSD) as compared with crystals produced in a stirred bulk crystallizer. By controlling the drop size and initial supersaturation the mean crystal size can be controlled. The distribution of the number of crystals per drop and the CSD are measured as a function of supersaturation at temperatures between 20 and for 150 and drops. In the case where drops contain only one crystal, a very narrow CSD is obtained with a coefficient of variation of crystal size as low as 7%. The crystallization of lactose in a microfluidic tubular crystallizer is modeled by treating nucleation in drops as a Poisson process with a nucleation rate based on classical nucleation theory. Experimental results are in good agreement with predictions from a Poisson process model over the range of temperatures, supersaturations and drop sizes tested. [Copyright &y& Elsevier]

Abstract: An algorithm has been developed to create structural models for amorphous carbons using Monte Carlo simulations in the canonical ensemble. The simulation method used follows the experimental preparation of nanoporous carbons (NPC) by pyrolysis from polyfurfuryl alcohol as a guideline. The resulting structure exhibits properties that compare favorably to those observed experimentally for real NPCs. These atomistic NPC models are approaching a realistic representation of NPCs used for gas separations and as such, are being used to study the diffusion of small gas molecules in these materials. Limitations of the method and possible improvements are discussed. [Copyright &y& Elsevier]

Small angle neutron scattering (SANS) studies of a model pharmaceutical formulation reveal how formulation stability depends on the compatibility of individual components. Solutions of two common protein formulation excipients, polysorbate 80 (PS80), a nonionic surfactant that prevents aggregation, and m-cresol, an antimicrobial agent for multi-dose injectable formulations, are investigated. The addition of m-cresol to PS80 solutions leads to solution turbidity and irreversibly alters PS80 micelle morphology. This slow preservative-induced destabilization of PS80 micelles progresses over days or even weeks, which highlights the essential role that aggregation kinetics plays in preservative-surfactant interactions. The temperature-dependence of PS80 micelle growth kinetics is quantified by SANS in the presence of m-cresol. Aggregation is a two-step process, where initial formation of small aggregates is followed by a period of monotonic power-law growth, providing evidence for the mechanism. Total aggregate mass stays constant after initial aggregate formation, and addition of a pH-regulating citrate buffer dramatically accelerates aggregation kinetics. [ABSTRACT FROM AUTHOR]

Surfactants are commonly used in therapeutic protein formulations in biopharmaceuticals to impart protein stability; however, their solution morphology and the role of the individual components in these structurally heterogeneous commercial grade surfactants at physiologically and pharmaceutically relevant temperatures have not been investigated systematically. The micellar morphologies of Polysorbate 20 and Polysorbate 80 and their primary components monoester fractions, as well as the diester fractions, are evaluated at 4, 22°C, 40°C, and 50°C using small-angle neutron scattering to determine the aggregation number, radius of gyration, core radius, critical micelle concentration, shell thickness, and shell hydration. The sizes and aggregation numbers of the diester fractions of PS20 above 80°C and PS80 above 50°C exhibit significant changes in shape. The analysis of the small-angle neutron scattering data of PS20 confirms that the critical micellar concentration of the monoester fraction is significantly higher at 4°C compared to the diester fraction and their original material, all-laurate PS20. Overall, these experiments identify the dominant components responsible for the temperature-dependent behavior of these surfactants in pharmaceutical protein formulations. [ABSTRACT FROM AUTHOR]

Mathematical modeling of drug release can aid in the design and development of sustained delivery systems, but the parameter estimation of such models is challenging owing to the nonlinear mathematical structure and complexity and interdependency of the physical processes considered. Highly parameterized models often lead to overfitting, strong parameter correlations, and as a consequence, inaccurate model predictions for systems not explicitly part of the fitting database. Here, we show that an efficient stochastic optimization algorithm can be used not only to find robust estimates of global minima to such complex problems but also to generate metadata that allow quantitative evaluation of parameter sensitivity and correlation, which can be used for further model refinement and development. A practical methodology is described through the analysis of a predictive drug release model on published experimental data sets. The model is then used to design a zeroth-order release profile in an experimental system consisting of an antibody fragment in a poly(lactic-co-glycolic acid) solvent depot, which is validated experimentally. This approach allows rational decision-making when developing new models, selecting models for a specific application, or designing formulations for experimental trials. [ABSTRACT FROM AUTHOR]

Understanding the adsorption of protein and surfactant molecules on hydrophobic surfaces is very important for storage stability and delivery of pharmaceutical liquid formulations as many commonly-used devices, such as drug containers and syringes, have hydrophobic surfaces. Neutron reflectometry is used here to investigate the structure information of the adsorption process of non-ionic surfactant (polysorbate 20) and proteins (monoclonal antibody (mAb) and lysozyme) on polystyrene surfaces. Thickness of adsorbed polysorbate 20 thin film is observed to be ≈21 Å, comparable to the radius of gyration of polysorbate 20 micelles in solution. Although no lysozyme adsorption is observed on the polystyrene surface in low solution pH condition, the mAb can be strongly absorbed on the polystyrene surface with a layer thickness of ≈145 Å. The mAb concentration near the surface is about 135 mg/ml significantly larger than the bulk protein concentration. The differences in adsorption behavior are attributed to different protein interactions with a hydrophobic surface. Further, both surfactants and proteins adsorbed on the polystyrene surfaces can not be rinsed off using pure water. [ABSTRACT FROM AUTHOR]

The low-earth orbit environment contains small micrometeoroid and orbital debris (MMOD) particles traveling at characteristic velocities of several kilometers per second. In addition to being a direct threat to astronauts and spacecraft, upon impact with the exterior surface of a space vehicle, these highly energetic MMOD particles can create cut and puncture hazards for astronauts performing extra-vehicular activities (EVA). In this work, we demonstrate that replacing the standard neoprene-coated nylon absorber layers with woven aramid textiles intercalated with colloidal shear thickening fluids, i.e., STF-Armor™, can provide a meaningful enhancement to the cut and puncture resistance of the thermal micrometeoroid garment (TMG). Quasi-static puncture testing is performed using hypodermic needles of varying gauge to simulate the cutting and puncture hazards at deformation rates characteristic of human motion. At equal areal densities, we find that a TMG lay-up containing STF-Armor™ greatly improves puncture protection with a reduction in weight and comparable flexibility. [ABSTRACT FROM AUTHOR]

Abstract: Targeted delivery of imaging agents to cells can be optimized with the understanding of uptake and efflux rates. Cellular uptake of macromolecules is studied frequently with fluorescent probes. We hypothesized that the internalization and efflux of fluorescently labeled macromolecules into and out of mammalian cells could be quantified by confocal microscopy to determine the rate of uptake and efflux, from which the mass transfer coefficient is calculated. The cellular influx and efflux of a third generation poly(amido amine) (PAMAM) dendrimer labeled with an Alexa Fluor 555 dye was measured in Capan-1 pancreatic cancer cells using confocal fluorescence microscopy. The Capan-1 cells were also labeled with 5-chloromethylfluorescein diacetate (CMFDA) green cell tracker dye to delineate cellular boundaries. A dilution curve of the fluorescently labeled PAMAM dendrimer enabled quantification of the concentration of dendrimer in the cell. A simple mass transfer model described the uptake and efflux behavior of the PAMAM dendrimer. The effective mass transfer coefficient was found to be 0.054±0.043μm/min, which corresponds to a rate constant of 0.035±0.023min−1 for uptake of the PAMAM dendrimer into the Capan-1 cells. The effective mass transfer coefficient was shown to predict the efflux behavior of the PAMAM dendrimer from the cell if the fraction of labeled dendrimer undergoing non-specific binding is accounted for. This work introduces a novel method to quantify the mass transfer behavior of fluorescently labeled macromolecules into mammalian cells. [Copyright &y& Elsevier]

Abstract: We present a simplified approach to understanding the mechanics of stable electrospinning jets based on electrohydrodynamic theory that explicitly incorporates the extensional rheology of polymeric fluids. Flow regimes of electrospun jets are identified by analogy to uniaxial extension of a fluid jet. These flow regimes predict the limiting kinematics of electrospinning jets and identify dimensionless parameters important to the control and operation of electrospinning processes. In situ kinematic measurements validate model assumptions and scaling predictions, and allow the reduction of entire jet radius and velocity profiles to several key parameters. The model predictions are shown to hold both above and below the entanglement concentration, as well as for solutions with added electrolyte and increased conductivity. The analysis also enables direct measurement of the apparent extensional viscosity of solutions at the high extension rates experienced during electrospinning. Finally, dimensional analysis of the model yields a correlation for electrospun fiber diameter in terms of measurable fluid properties, controlled process parameters, and measured jet variables, demonstrating the influence of mechanics in the straight portion of the jet on ultimate fiber morphology. [Copyright &y& Elsevier]