Defining Structure-Function Relationships of Amphiphilic Excipients Enables Rational Design of Ultra-Stable Biopharmaceuticals.

Biopharmaceuticals are the fastest-growing class of drugs in the healthcare industry, but their global reach is severely limited by their propensity for rapid aggregation. Currently, surfactant excipients such as polysorbates and poloxamers are used to prevent protein aggregation, which significantly extends shelf-life. Unfortunately, these excipients are themselves unstable, oxidizing rapidly into 100s of distinct compounds, some of which cause severe adverse events in patients.

Magnetic microwire rheometer reveals differences in hydrogel degradation disulfide reducing agents.

Mucus is composed of a complex network of mucin polymers connected by disulfide bonds. In muco-obstructive diseases, an increase in mucin disulfide crosslinks contributes to pathologic mucus formation, characterized by an increase in mucus viscosity and stiffness. Reducing agents that break down the disulfide bonds between mucins can be used to treat pathologic mucus and restore healthy mucus flow properties.

Elucidating the roles of electrolytes and hydrogen bonding in the dewetting dynamics of the tear film.

This study explores the impact of electrostatic interactions and hydrogen bonding on tear film stability, a crucial factor for ocular surface health. While mucosal and meibomian layers have been extensively studied, the role of electrolytes in the aqueous phase remains unclear. Dry eye syndrome, characterized by insufficient tear quantity or quality, is associated with hyperosmolality, making electrolyte composition an important factor that might impact tear stability.

Peroxidase-mediated mucin cross-linking drives pathologic mucus gel formation in IL-13-stimulated airway epithelial cells.

Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and studies in human airway epithelial cells (HAECs) show that IL-13-activated cells generate pathologic mucus independently of immune cells. To determine how HAECs autonomously generate pathologic mucus, we used a magnetic microwire rheometer to characterize the viscoelastic properties of mucus secreted under varying conditions.

Air-liquid intestinal cell culture allows rheological characterization of intestinal mucus.

Intestinal health heavily depends on establishing a mucus layer within the gut with physical properties that strike a balance between being sufficiently elastic to keep out harmful pathogens yet viscous enough to flow and turnover the contents being digested. Studies investigating dysfunction of the mucus layer in the intestines are largely confined to animal models, which require invasive procedures to collect the mucus fluid. In this work, we develop a nondestructive method to study intestinal mucus.

Response of lymphatic endothelial cells to combined spatial and temporal variations in fluid flow.

One-way valves within lymphatic vessels are required for the efficient drainage of lymphatic fluids. Fluid flow is proposed to be a key cue in regulating both the formation and maintenance of lymphatic valves. However, to our knowledge, no previous study has systematically examined the response of LECs to the complex combination of spatially and temporally varying fluid flows that occur at lymphatic valves in vivo.

The Role of Membrane-Tethered Mucins in Axial Epithelial Adhesion in Controlled Normal Stress Environments.

The collective adhesive behavior of epithelial cell layers mediated by complex macromolecular fluid environments plays a vital role in many biological processes. Mucins, a family of highly glycosylated proteins, are known to lubricate cell-on-cell contacts in the shear direction. However, the role of mucins mediating axial epithelial adhesion in the direction perpendicular to the plane of the cell sheet has received less attention.

Coalescence of surface bubbles: The crucial role of motion-induced dynamic adsorption layer.

The formation of motion-induced dynamic adsorption layers of surfactants at the surface of rising bubbles is a widely accepted phenomenon. Although their existence and formation kinetics have been theoretically postulated and confirmed in many experimental reports, the investigations primarily remain qualitative in nature. In this paper we present results that, to the best of our knowledge, provide a first quantitative proof of the influence of the dynamic adsorption layer on drainage dynamics of a single foam film formed under dynamic conditions.

Stable High-Concentration Monoclonal Antibody Formulations Enabled by an Amphiphilic Copolymer Excipient.

Monoclonal antibodies are a staple in modern pharmacotherapy. Unfortunately, these biopharmaceuticals are limited by their tendency to aggregate in formulation, resulting in poor stability and often requiring low concentration drug formulations. Moreover, existing excipients designed to stabilize these formulations are often limited by their toxicity and tendency to form particles such as micelles.

Effect of Recombinant Human Lubricin on Model Tear Film Stability.

Purpose: To investigate and quantify the effect of recombinant human lubricin (rh-lubricin) on model tear film stability.

Methods: A custom-built, interferometry-based instrument called the Interfacial Dewetting and Drainage Optical Platform was used to create and record the spatiotemporal evolution of model acellular tear films. Image segmentation and analysis was performed in MATLAB to extract the most essential features from the wet area fraction versus time curve, namely the evaporative break-up time and the final wet area fraction (A10).

Tear Film Stability as a Function of Tunable Mucin Concentration Attached to Supported Lipid Bilayers.

In this work, we describe the development of a tunable, acellular model of the mucin layer of the human tear film. First, supported lipid bilayers (SLBs) comprised of the phospholipid DOPC (1,2-dioleoyl--glycero-3-phosphocholine) and biotinyl cap PE (1,2-dioleoyl--glycero-3-phosphoethanolamine-N-(cap biotinyl)) are created on the surface of a glass dome with radius of curvature comparable to the human eye. Next, biotinylated bovine submaxillary mucins (BSM) are tethered onto the SLB using streptavidin protein.

Systematic characterization of effect of flow rates and buffer compositions on double emulsion droplet volumes and stability.

Double emulsion droplets (DEs) are water/oil/water droplets that can be sorted fluorescence-activated cell sorting (FACS), allowing for new opportunities in high-throughput cellular analysis, enzymatic screening, and synthetic biology. These applications require stable, uniform droplets with predictable microreactor volumes. However, predicting DE droplet size, shell thickness, and stability as a function of flow rate has remained challenging for monodisperse single core droplets and those containing biologically-relevant buffers, which influence bulk and interfacial properties.

A Mucin-Deficient Ocular Surface Mimetic Platform for Interrogating Drug Effects on Biolubrication, Antiadhesion Properties, and Barrier Functionality.

Dry eye disease (DED) affects more than 100 million people worldwide, causing significant patient discomfort and imposing a multi-billion-dollar burden on global health care systems. In DED patients, the natural biolubrication process that facilitates pain-free blinking goes awry due to an imbalance of lipids, aqueous medium, and mucins in the tear film, resulting in ocular surface damage. Identifying strategies to reduce adhesion and shear stresses between the ocular surface and the conjunctival cells lining the inside of the eyelid during blink cycles is a promising approach to improve the signs and symptoms of DED.

Flowering in bursting bubbles with viscoelastic interfaces.

The lifetime of bubbles, from formation to rupture, attracts attention because bubbles are often present in natural and industrial processes, and their geometry, drainage, coarsening, and rupture strongly affect those operations. Bubble rupture happens rapidly, and it may generate a cascade of small droplets or bubbles. Once a hole is nucleated within a bubble, it opens up with a variety of shapes and velocities depending on the liquid properties.

Engineering Insulin Cold Chain Resilience to Improve Global Access.

There are 150 million people with diabetes worldwide who require insulin replacement therapy, and the prevalence of diabetes is rising the fastest in middle- and low-income countries. The current formulations require costly refrigerated transport and storage to prevent loss of insulin integrity. This study shows the development of simple "drop-in" amphiphilic copolymer excipients to maintain formulation integrity, bioactivity, pharmacokinetics, and pharmacodynamics for over 6 months when subjected to severe stressed aging conditions that cause current commercial formulation to fail in under 2 weeks.

Mucin-Like Glycoproteins Modulate Interfacial Properties of a Mimetic Ocular Epithelial Surface.

Dry eye disease (DED) has high personal and societal costs, but its pathology remains elusive due to intertwined biophysical and biochemical processes at the ocular surface. Specifically, mucin deficiency is reported in a subset of DED patients, but its effects on ocular interfacial properties remain unclear. Herein a novel in vitro mucin-deficient mimetic ocular surface (Mu-DeMOS) with a controllable amount of membrane-tethered mucin molecules is developed to represent the diseased ocular surfaces.

Adsorption and Aggregation of Monoclonal Antibodies at Silicone Oil-Water Interfaces.

Monoclonal antibody (mAb) therapies are rapidly growing for the treatment of various diseases like cancer and autoimmune disorders. Many mAb drug products are sold as prefilled syringes and vials with liquid formulations. Typically, the walls of prefilled syringes are coated with silicone oil to lubricate the surfaces during use.

In-Use Interfacial Stability of Monoclonal Antibody Formulations Diluted in Saline i.v. Bags.

The use of monoclonal antibodies (mAbs) for the treatment of a variety of diseases is rapidly growing each year. Many mAbs are administered intravenously using i.v.

Tuning corneal epithelial cell adhesive strength with varying crosslinker content in silicone hydrogel materials.

Purpose: To quantify the effect of silicone hydrogel crosslink density on the adhesion at corneal epithelial cells/silicone hydrogel contact lens interface.

Methods: A custom-built rheometer, referred to as the live cell monolayer rheometer, was used to measure the adhesive strengths between corneal epithelial cell monolayers and silicone hydrogel lens surfaces. The resulting stress relaxations of senofilcon A-derived silicone hydrogel materials with varying crosslinking densities and delefilcon A were tested.

Understanding the adsorption and potential tear film stability properties of recombinant human lubricin and bovine submaxillary mucins in an in vitro tear film model.

The wetting and adsorption properties for two glycoproteins, recombinant human lubricin and bovine submaxillary mucins (BSM) were evaluated on hydrophilic and hydrophobic glass dome surfaces in a simplified in vitro tear film model. We show that both recombinant human lubricin (rh-lubricin) and BSM solutions render surfaces hydrophilic and when the fluid films reach 500 nm or less, the fluids resist evaporation-driven breakup through a volumetric flux across the surface, which we believe is due to evaporation-driven solutocapillary flows. rh-Lubricin was able to maintain a wet film without spontaneous breakup for longer periods of time than BSM at lower concentrations, which we attribute to differences in adsorption properties, measured by QCM-D, that result from surface charge and structural differences (confirmed by zeta potential, DLS, and SAXS measurements).

Evaporation-induced Rayleigh-Taylor instabilities in polymer solutions.

Understanding the mechanics of detrimental convective instabilities in drying polymer solutions is crucial in many applications such as the production of film coatings. It is well known that solvent evaporation in polymer solutions can lead to Rayleigh-Bénard or Marangoni-type instabilities. Here, we reveal another mechanism, namely that evaporation can cause the interface to display Rayleigh-Taylor instabilities due to the build-up of a dense layer at the air-liquid interface.

Correction: Viscoelastic interfaces comprising of cellulose nanocrystals and lauroyl ethyl arginate for enhanced foam stability.

Correction for 'Viscoelastic interfaces comprising of cellulose nanocrystals and lauroyl ethyl arginate for enhanced foam stability' by Agnieszka Czakaj et al., Soft Matter, 2020, 16, 3981-3990, DOI: .

Polymeric-nanofluids stabilized emulsions: Interfacial versus bulk rheology.

Hypothesis: The properties of oil-in-water emulsions are influenced by the rheology of the aqueous phase (continuous phase) and the rheology of the oil-water interfaces. The bulk and interfacial rheological parameters can be tuned by incorporating nanoparticles (NPs) featuring different surface chemistries and polymers with different chemical or physical structures. Therefore, NPs and polymers can be used to formulate emulsions with different properties.

Surfactant-laden bubble dynamics under porous polymer films.

The dynamics of air bubbles spreading on the underside of solid substrates is an important scientific problem with numerous applications. This work explores the spreading of bubbles against an ultra-thin, porous ultra-high-molecular-weight polyethylene (UHMWPE) film. This polymer film can be used in applications where a solid-liquid-gas interface is involved, like froth flotation for mineral processing, underwater methane capture, to prevent foaming in bioreactors, and in degassing in microfluidics.