Curcumin exerts a wide range of beneficial physiological and pharmacological activities, including antioxidant, anti-amyloid, anti-inflammatory, anti-microbial, anti-neoplastic, immune-modulating, metabolism regulating, anti-depressant, neuroprotective and tissue protective effects. However, its poor solubility and poor absorption in the free form in the gastrointestinal tract and its rapid biotransformation to inactive metabolites greatly limit its utility as a health-promoting agent and dietary supplement. Recent advances in micro- and nano-formulations of curcumin with greatly enhanced absorption resulting in desirable blood levels of the active forms of curcumin now make it possible to address a wide range of potential applications, including pain management, and as tissue protective. Using these forms of highly bioavailable curcumin now enable a broad spectrum of appropriate studies to be conducted. This review discusses the formulations designed to enhance bioavailability, metabolism of curcumin, relationships between solubility and particle size relative to bioavailability, human pharmacokinetic studies involving formulated curcumin products, the widely used but inappropriate practice of hydrolyzing plasma samples for quantification of blood curcumin, current applications of curcumin and its metabolites and promising directions for health maintenance and applications.
We have developed an integrated label-free, real-time sensing system that is able to monitor multiple biomolecular binding events based on the changes in the intensity of extraordinary optical transmission (EOT) through nanohole arrays. The core of the system is a sensing chip containing multiple nanohole arrays embedded within an optically thick gold film, where each array functions as an independent sensor. Each array is a square array containing 10 x 10 nanoholes (150 nm in diameter), occupying a total area of 3.3 mum x 3.3 mum. The integrated system includes a laser light source, a temperature-regulated flow cell encasing the sensing chip, motorized optics, and a charge-coupled detector (CCD) camera. For demonstration purposes, sensing chips containing 25 nanohole arrays were studied for their use in multiplexed detection, although the sensing chip could be easily populated to contain up to 20 164 nanohole arrays within its 0.64 cm2 sensing area. Using this system, we successfully recorded 25 separate binding curves between glutathione S-transferase (GST) and anti-GST simultaneously in real time with good sensitivity. The system responds to binding events in a concentration-dependent manner, showing a sharp linear response to anti-GST at concentrations ranging from 13 to 290 nM. The EOT intensity-based approach also enables the system to monitor multiple bindings simultaneously and continuously, offering a temporal resolution on milliseconds scale that is decided only by the camera speed and exposure time. The small footprint of the sensing arrays combined with the EOT intensity-based approach enables the system to resolve binding events that occurred on nanohole sensing arrays spaced 96 mum apart, with a reasonable prediction of resolving binding events spaced 56 mum apart. This work represents a new direction that implements nanohole arrays and EOT intensity to meet high-throughput, spatial and temporal resolution, and sensitivity requirements in drug discovery and proteomics studies.
This paper describes the synthesis and characterization of micrometric phospholipid-coated polystyrene particles, named lipobeads, with pH-sensing capability and their application for intracellular pH measurements in murine macrophages. The phospholipids used to coat the particles are labeled with fluorescein (a pH-sensitive dye) and tetramethylrhodamine (a pH-insensitive dye), which serves as a referencing fluorophore for increased accuracy of the pH measurements. The synthesis of the pH-sensing lipobeads is realized by the covalent attachment of the fluorescent phospholipids to the surface of carboxylated polystyrene particles. The pH dynamic range of the sensing particles is between 5.5 and 7.0 with a sensitivity of 0.1 pH unit. The excitation light intensity is reduced to minimize photobleaching of the fluorescein-phospholipid conjugates. The fluorescent lipobeads are used to measure the pH in single macrophages. The lipobeads are ingested by the macrophages and directed to lysosomes, which are the cellular organelles involved in the phagocytosis process. Despite the high lysosomal levels of digestive enzymes and acidity, the absorbed particles remain stable for over 6 h in the cells when they are stored in a phosphate-buffered saline solution at pH 7.4.
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