A Simple Method for Synthesis of Chitosan Nanoparticles with Ionic Gelation and Homogenization.

Chitosan nanoparticles (CNPs) are known to have great utility in many fields (pharmaceutical, agricultural, food industry, wastewater treatment, etc.). In this study we aimed to synthesize sub-100 nm CNPs as a precursor of new biopolymer-based virus surrogates for water applications. We present a simple yet efficient synthesis procedure for obtaining high yield, monodisperse CNPs with size 68-77 nm. The CNPs were synthesized by ionic gelation using low molecular weight chitosan (deacetylation 75-85%) and tripolyphosphate as crosslinker, under rigorous homogenization to decrease size and increase uniformity, and purified by passing through 0.1 µm polyethersulfone syringe filters. The CNPs were characterized using dynamic light scattering, tunable resistive pulse sensing, and scanning electron microscopy. We demonstrate reproducibility of this method at two separate facilities. The effects of pH, ionic strength and three different purification methods on the size and polydispersity of CNP formation were examined. Larger CNPs (95-219) were produced under ionic strength and pH controls, and when purified using ultracentrifugation or size exclusion chromatography. Smaller CNPs (68-77 nm) were formulated using homogenization and filtration, and could readily interact with negatively charge proteins and DNA, making them an ideal precursor for the development of DNA-labelled, protein-coated virus surrogates for environmental water applications.

Synthesis of Alginate Nanoparticles Using Hydrolyzed and Enzyme-Digested Alginate Using the Ionic Gelation and Water-in-Oil Emulsion Method.

Alginate nanoparticles (AlgNPs) are attracting increasing interest for a range of applications because of their good biocompatibility and their ability to be functionalized. Alginate is an easily accessible biopolymer which is readily gelled by the addition of cations such as calcium, facilitating a cost-effective and efficient production of nanoparticles. In this study, AlgNPs based on acid hydrolyzed and enzyme-digested alginate were synthesized by using ionic gelation and water-in-oil emulsification, with the goal to optimize key parameters to produce small uniform (<200 nm) AlgNPs. By the ionic gelation method, such AlgNPs were obtained when sample concentrations were 0.095 mg/mL for alginate and CaCl2 in the range of 0.03-0.10 mg/mL. Alginate and CaCl2 concentrations > 0.10 mg/mL resulted in sizes > 200 nm with relatively high dispersity. Sonication in lieu of magnetic stirring proved to further reduce size and increase homogeneity of the nanoparticles. In the water-in-oil emulsification method, nanoparticle growth was confined to inverse micelles in an oil phase, resulting in lower dispersity. Both the ionic gelation and water-in-oil emulsification methods were suitable for producing small uniform AlgNPs that can be further functionalized as required for various applications.

Pulmonary surfactant function and molecular architecture is disrupted in the presence of vaping additives.

Inhalation of harmful vaping additives has led to a series of lung illnesses. Some of the selected additives such as vitamin E acetate, and related molecules like vitamin E and cannabidiol, may interfere with the function of the lung surfactant. Proper lipid organization in lung surfactant is key to maintaining low surface tensions, which provides alveolar stability and effective gas exchange throughout respiration. Physiological surfactants, such as bovine lipid extract surfactant used to treat neonatal respiratory distress syndrome, serve as a good model for examining the potential effects of vape additives on proper function. We have found that all additives impede the surfactants' ability to efficiently reach high surface pressures as these systems displayed numerous shoulders throughout compression with accompanying defects to lipid organization. Moreover, the formation of lipid bilayer stacks in the film are hindered by the additives, most notably with vitamin e acetate. Loss of these stacks leave the film prone to buckling and collapse under high compression that occurs at the end of expiration. The data suggest that the additives may interfere with both proper lipid organization and the surfactant protein function.

Vaping additives negatively impact the stability and lateral film organization of lung surfactant model systems.

Aims: Inhalation of vaping additives has recently been shown to impair respiratory function, leading to e-cigarette or vaping product use associated with lung injuries. This work was designed to understand the impact of additives (vitamin E, vitamin E acetate, tetrahydrocannabinol and cannabidiol) on model lung surfactants. Materials & methods: Lipid monofilms at the air-water interface and Brewster angle microscopy were used to assess the impact of vaping additives on model lung surfactant films. Results & conclusion: The addition of 5 mol % of vaping additives, and even more so mixtures of vitamins and cannabinoids, negatively impacts lipid packing and film stability, induces material loss upon cycling and significantly reduces functionally relevant lipid domains. This range of detrimental effects could affect proper lung function.

The increasing use of vaping products in young adults and the emergence of associated lung injuries have resulted in significant health concerns for healthcare professionals and the public alike. These detrimental effects were linked to additives such as vitamin E and cannabinoids. The deep lung is composed of many small compartments, where oxygen is taken up into the body. The ultimate barrier between the outer gas phase and the lung cells is a layer composed of mainly lipids and some proteins, the lung surfactant. The authors present data for lung surfactant models based on the composition of human lung surfactant. The selected components reflect key lung surfactant roles, stability upon exhalation and fast spreading after inhalation. Additives have recently been shown to impair respiratory function, leading to e-cigarette or vaping product use associated lung injuries. This work was designed to understand the impact of additives (vitamin E, vitamin E acetate, tetrahydrocannabinol and cannabidiol) on model lung surfactants. All tested additives, and more so their mixtures, clearly affected the lung surfactant model in terms of stability and elasticity, which impairs its ability to perform the aforementioned roles. Lipid monofilms at the air­water interface and Brewster angle microscopy were used to assess the impact of vaping additives on model lung surfactant films. The addition of 5 mol % of vaping additives, and even more so mixtures of vitamins and cannabinoids, negatively impacts lipid packing and film stability, induces material loss upon cycling and significantly reduces functionally relevant lipid domains. This range of detrimental effects could affect proper lung function.

Collagen - a newly discovered major player in protein corona formation on nanoparticles.

Tracking protein corona (PC) formation on the surface of nanoparticles (NPs) is a prerequisite for successful design of next generation nanocarriers with predictable fate and behavior. However, PC formation has mostly been investigated for plasma proteins without considering potential competition with the extravascular proteins either when the NPs exit the blood circulation or when they are injected extravascularly. This study investigates the deposition of collagen, an extravascular protein that is the most abundant in the body, and albumin, the most abundant vascular protein, on the surface of gold (Au) NPs using UV-Vis and fluorescence spectroscopy with the support of mathematical modeling. Moreover, a novel spectroscopic approach to determining the protein-NP binding constants and surface occupancy is presented. We show that albumin and collagen have drastically different affinities for Au NPs. Our data demonstrates that the surface bound albumin can be exchanged with collagen confirming the dynamic nature of PC in the extravascular milieu. We propose that future PC investigations in the framework of drug delivery should rely on understanding of the NP transit in the body, and include competition experiments with relevant vascular and extravascular proteins. Furthermore, our results that reveal very strong binding of collagen to AuNPs may lay the foundation for designing long circulating collagen-coated NPs with minimal surface adsorption of plasma proteins and, thus, reduced immune recognition.

Benefits and Detriments of Gadolinium from Medical Advances to Health and Ecological Risks.

Gadolinium (Gd)-containing chelates have been established as diagnostics tools. However, extensive use in magnetic resonance imaging has led to increased Gd levels in industrialized parts of the world, adding to natural occurrence and causing environmental and health concerns. A vast amount of data shows that metal may accumulate in the human body and its deposition has been detected in organs such as brain and liver. Moreover, the disease nephrogenic systemic fibrosis has been linked to increased Gd3+ levels. Investigation of Gd3+ effects at the cellular and molecular levels mostly revolves around calcium-dependent proteins, since Gd3+ competes with calcium due to their similar size; other reports focus on interaction of Gd3+ with nucleic acids and carbohydrates. However, little is known about Gd3+ effects on membranes; yet some results suggest that Gd3+ interacts strongly with biologically-relevant lipids (e.g., brain membrane constituents) and causes serious structural changes including enhanced membrane rigidity and propensity for lipid fusion and aggregation at much lower concentrations than other ions, both toxic and essential. This review surveys the impact of the anthropogenic use of Gd emphasizing health risks and discussing debilitating effects of Gd3+ on cell membrane organization that may lead to deleterious health consequences.