Urine metabolomics has recently emerged as a prominent field for the discovery of non-invasive biomarkers that can detect subtle metabolic discrepancies in response to a specific disease or therapeutic intervention. Urine, compared to other biofluids, is characterized by its ease of collection, richness in metabolites and its ability to reflect imbalances of all biochemical pathways within the body. Following urine collection for metabolomic analysis, samples must be immediately frozen to quench any biogenic and/or non-biogenic chemical reactions. According to the aim of the experiment; sample preparation can vary from simple procedures such as filtration to more specific extraction protocols such as liquid-liquid extraction. Due to the lack of comprehensive studies on urine metabolome stability, higher storage temperatures (i.e. 4 °C) and repetitive freeze-thaw cycles should be avoided. To date, among all analytical techniques, mass spectrometry (MS) provides the best sensitivity, selectivity and identification capabilities to analyze the majority of the metabolite composition in the urine. Combined with the qualitative and quantitative capabilities of MS, and due to the continuous improvements in its This is the peer reviewed version of: Khamis, M. M., Adamko, D. J. and El-Aneed, A. (2015), Mass Spec Rev., published in final form at https://doi.org/10.1002/mas.21455. [HILIC]), liquid chromatography (LC)-MS is unequivocally the most utilized and the most informative analytical tool employed in urine metabolomics. Furthermore, differential isotope tagging techniques has provided a solution to ion suppression from urine matrix thus allowing for quantitative analysis. In addition to LC-MS, other MS-based technologies have been utilized in urine metabolomics. These include direct injection (infusion)-MS, capillary electrophoresis-MS and gas chromatography-MS. In this article, the current progresses of different MS-based techniques in exploring the urine metabolome as well as the recent findings in providing potentially diagnostic urinary biomarkers are discussed.
Mass spectrometry (MS) has become an integral tool in life sciences. The first step in MS analysis is ion formation (ionization). Many ionization methods currently exist; electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) are the most commonly used. ESI relies on the formation of charged droplets releasing ions from the surface (ion evaporation model) or via complete solvent evaporation (charge residual model). MALDI ionization, however, is facilitated via laser energy and the use of a matrix. Despite wide use, ESI cannot efficiently ionize nonpolar compounds. Atmospheric pressure chemical ionization (APCI) and atmospheric pressure photo ionization (APPI) are better suited for such tasks. APPI requires photon energy and a dopant, whereas APCI is similar to chemical ionization. In 2004, ambient MS was introduced in which ionization occurs at the sample in its native form. Desorption electrospray ionization (DESI) and direct analysis in real time (DART) are the most widely used methods. In this mini-review, we provide an overview of the main ionization methods and the mechanisms of ion formation. This article is educational and intended for students/researchers who are not very familiar with MS and would like to learn the basics; it is not for MS experts.
Lipid-based drug-delivery systems have evolved from micro- to nano-scale, enhancing the efficacy and therapeutic applications of these delivery systems. Production of lipid-based pharmaceutical nanoparticles is categorized into top-down (fragmentation of particulate material to reduce its average total dimensions) and bottom-up (amalgamation of molecules through chemical interactions creating particles of greater size) production methods. Selection of the appropriate method depends on the physiochemical properties of individual entities within the nanoparticles. The production method also influences the type of nanoparticle formulations being produced. Liposomal formulations and solid-core micelles are the most widely utilized lipid-based nanoparticles, with surface modifications improving their therapeutic outcomes through the production of long-circulating, tissue-targeted and/or pH-sensitive nanoparticles. More recently, solid lipid nanoparticles have been engineered to reduce toxicity toward mammalian cells, while multifunctional lipid-based nanoparticles (i.e., hybrid lipid nanoparticles) have been formulated to simultaneously perform therapeutic and diagnostic functions. This article will discuss novel lipid-based drug-delivery systems, outlining the properties and applications of lipid-based nanoparticles alongside their methods of production. In addition, a comparison between generations of the lipid-based nano-formulations is examined, providing insight into the current directions of lipid-based nanoparticle drug-delivery systems.
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