Trapped and Alone: Clay-Assisted Aqueous Graphene Dispersions.

Dispersing graphene sheets in liquids, in particular water, could enhance the transport properties (like thermal conductivity) of the dispersion. Yet, such dispersions are difficult to achieve since graphene sheets are prone to aggregate and subsequently precipitate due to their strong van der Waals interactions. Conventional dispersion approaches, such as surface treatment of the sheets either by surfactant adsorption or by chemical modification, may prevent aggregation. Unfortunately, surfactant-assisted graphene dispersions are typically of low concentration (<0.2 wt %) with relatively small sheets (<1 µm lateral size) while chemical modification is punished by increased defect density within the sheets. We investigate here a new approach in which the concentration of dispersed graphene in water is enhanced by the addition of a fibrous clay mineral, sepiolite. As we demonstrate, the clay particles in water form a kinetically arrested particle network within which the graphene sheets are effectively trapped. This mechanism keeps graphene sheets of high lateral size (∼4 µm) dispersed at high concentrations (∼1 wt %). We demonstrate the application of such dispersions as cooling liquids for thermal management solutions, where a 26% enhancement in the thermal conductivity is achieved as compared to that in a filler-free fluid.

Vegetable-Oil-Based Intelligent Ink for Oxygen Sensing.

An oil-based composite is employed to monitor the exposure to oxygen inside food packaging, aiming at evaluating the package integrity and the freshness of food. The composite is an oxygen-sensitive printable ink consisting of electrically conductive silver microflakes, embedded in a vegetable oil matrix. The sensitivity of the oil to oxygen is driven by its high content of unsaturated fatty acids that polymerize and shrink upon exposure to atmospheric oxygen. Shrinkage increases the silver concentration and induces percolation, manifested by a steep increase in the electrical conductivity of the composite. We found that the electrical conductivity of the composite is related to its exposure time to air. Employing linseed oil as a matrix demonstrates an increase in electrical conductivity from 10-11 to 10-3 S/cm after only 6 days of exposure to air. We also show that this time span could be modified by changing the oil type to fit various expiration periods of food products.

Sensing Exposure Time to Oxygen by Applying a Percolation-Induced Principle.

The determination of food freshness along manufacturer-to-consumer transportation lines is a challenging problem that calls for cheap, simple, reliable, and nontoxic sensors inside food packaging. We present a novel approach for oxygen sensing in which the exposure time to oxygen-rather than the oxygen concentration per se-is monitored. We developed a nontoxic hybrid composite-based sensor consisting of graphite powder (conductive filler), clay (viscosity control filler) and linseed oil (the matrix). Upon exposure to oxygen, the insulating linseed oil is oxidized, leading to polymerization and shrinkage of the matrix and hence to an increase in the concentration of the electrically conductive graphite powder up to percolation, which serves as an indicator of food spoilage. In the developed sensor, the exposure time to oxygen (days to weeks) is obtained by measuring the electrical conductivity though the sensor. The sensor functionality could be tuned by changing the oil viscosity, the aspect ratio of the conductive filler, and/or the concentration of the clay, thereby adapting the sensor to monitoring the quality of food products with different sensitivities to oxygen exposure time (e.g., fish vs grain).

Cardinal Role of Intraliposome Doxorubicin-Sulfate Nanorod Crystal in Doxil Properties and Performance.

The uniqueness of Doxil can be attributed, to a large extent, to its intraliposomal doxorubicin-sulfate nanorod crystal. We re-examine these nanocrystal features and their mechanism of the formation by studying pegylated liposomal doxorubicins (PLDs) of the same lipid composition, size distribution, and extraliposome medium that were prepared at different ammonium sulfate (AS) concentrations. This study includes a comparison of the thermotropic behavior, morphology, and in vitro ammonia-induced doxorubicin release (relevant to Doxil's in vivo performance) of these PLDs. In this study, we confirm that a transmembrane ammonium gradient is critical for doxorubicin remote loading, and we demonstrate that the intraliposomal concentration of sulfate counteranions and ammonium ions determine to a large extent the physical state and stability of the PLDs' remote loaded doxorubicin. "Fully-developed" intraliposome doxorubicin-sulfate nanorod crystals (as defined by cryogenic transmission electron microscopy imaging) develop only when the ammonium sulfate (AS) concentration used for PLD preparation is ≥150 mM. Less than 10% of PLDs prepared with 100 mM AS show fully developed nanorod crystals. Intraliposomal AS concentration ≥200 mM is required to support the stable nanocrystallization in PLDs. The presence of nanocrystals and their melting enthalpy and phase transition co-operativity strongly affect the ammonia-induced doxorubicin release of PLDs. A quick, biphasic release occurs for PLDs that lack the nanorod crystals or have crystals of poor crystallinity, whereas PLDs prepared with ≥200 mM AS show a monophasic, zero-order slow release. This study also demonstrates that after remote loading, residual intraliposomal ammonium concentration and the transmembrane pH gradient related to it also play an important role in doxorubicin-sulfate intraliposomal crystallization and ammonia-induced doxorubicin release.

Practical aspects in size and morphology characterization of drug-loaded nano-liposomes.

Size and morphology distributions are critical to the performance of nano-drug systems, as they determine drug pharmacokinetics and biodistribution. Therefore, comprehensive and reliable analyses of these properties are required by both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). In this study, we compare two most commonly used approaches for assessing the size distribution and morphology of liposomal nano-drug systems, namely, dynamic light scattering (DLS) and cryogenic-transmission electron microscopy (cryo-TEM); an automated quantitative analysis method was developed for the latter method. We demonstrate the advantages and disadvantages of each of these two approaches for a commercial formulation of the anti-cancer drug doxorubicin - Doxil®, in which the drug is encapsulated, mostly in the form of nano-rod crystals. With increasing drug concentration, these nano-rods change the shape of the liposomes from spherical, before drug loading, to prolate (oval), post drug loading. Cryo-TEM analysis provides a detailed size distribution of both the liposomes (minor and major axes) and the nano-rod drug. Both these values are relevant to the drug performance. In this study, we show that at elevated drug concentration (2.75 mg/ml) the drug grows mainly along the major axis and that this high concentration can result, in some cases, in liposome rupture. We show that the combination of cryo-TEM and DLS constitutes a reliable tool for demonstrating the stability of the formulation in human plasma at body temperature, a characteristic that is crucial for achieving therapeutic efficacy.