Current Issue : January - March Volume : 2020 Issue Number : 1 Articles : 5 Articles
Nanotechnology is being increasingly utilised in medicine as diagnostics and for drug\ndelivery and targeting. The small size and high surface area of nanoparticles (NPs), desirable\nproperties that allow them to cross biological barriers, also offer potential for interaction with other\ncells and blood constituents, presenting possible safety risks. While NPs investigated are\npredominantly based on the biodegradable, biocompatible, and FDA approved\npoly-lactide-co-glycolide (PLGA) polymers, pro-aggregatory and antiplatelet effects have been\nreported for certain NPs. The potential for toxicity of PLGA based NPs remains to be examined.\nThe aims of this study were to determine the impact of size-selected PLGA-PEG\n(PLGA-polyethylene glycol) NPs on platelet activation and aggregation. PLGA-PEG NPs of three\naverage sizes of 112, 348, and 576 nm were formulated and their effect at concentrations of 0.0-2.2\nmg/mL on the activation and aggregation of washed human platelets (WP) was examined. The\nresults of this study show, for the first time, NPs of all sizes associated with the surface of platelets,\nwith >50% binding, leading to possible internalisation. The NP-platelet interaction, however, did\nnot lead to platelet aggregation nor inhibited aggregation of platelets induced by thrombin. The\noutcome of this study is promising, suggesting that these NPs could be potential carriers for\ntargeted drug delivery to platelets....
A wooden stick coated with a novel graphene-based nanocomposite (Graphene\noxide/polyethylene glycol (GO/PEG)) is introduced and investigated for its efficacy in solid\nphase microextraction techniques. The GO/PEG-stick was prepared and subsequently applied\nfor the extraction of Beta-blockers, acebutolol, and metoprolol in human oral fluid samples, which\nwere subsequently detected by liquid chromatography tandem mass spectrometry (LC-MS/MS).\nExperimental parameters affecting the extraction protocol including sample pH, extraction time,\ndesorption time, appropriate desorption solvent, and salt addition were optimized. Method\nvalidation for the detection from oral fluid samples was performed following FDA (Food and\nDrug Administration) guidelines on bioanalytical method validation. Calibration curves ranging\nfrom 5.0 to 2000 nmol L-1 for acebutolol and 25.0 to 2000 nmol L-1 for metoprolol were used.\nThe values for the coefficient of determination (R2) were found to be 0.998 and 0.996 (n = 3) for\nacebutolol and metoprolol, respectively. The recovery of analytes during extraction was 80.0%\nfor acebutolol and 62.0% for metoprolol, respectively. The limit of detections (LODs) were 1.25,\n8.00 nmol L-1 for acebutolol and metoprolol and the lower limit of quantifications (LLOQ) were\n5.00 nmol L-1 for acebutolol and 25.0 nmol L-1 for metoprolol. Validation experiments conducted\nwith quality control (QC) samples demonstrated method accuracy between 80.0% to 97.0% for\nacebutolol and from 95.0% to 109.0% for metoprolol. The inter-day precision for QC samples ranged\nfrom 3.6% to 12.9% for acebutolol and 9.5% to 11.3% for metoprolol. Additionally, the GO/PEG-stick\nwas demonstrated to be reusable, with the same stick observed to be viable for more than 10 extractions\nfrom oral fluid samples....
Alzheimerâ??s disease (AD) is the most common form of dementia worldwide and is\ncharacterized by progressive cognitive decline. Along with being incurable and lethal, AD is difficult\nto diagnose with high levels of accuracy. Blood serum from Alzheimerâ??s disease (AD) patients was\nanalyzed by surface-enhanced Raman spectroscopy (SERS) coupled with multivariate statistical\nanalysis. The obtained spectra were compared with spectra from healthy controls (HC) to develop\na simple test for AD detection. Serum spectra from AD patients were further compared to spectra from\npatients with other neurodegenerative dementias (OD). Colloidal silver nanoparticles (AgNPs) were\nused as the SERS-active substrates. Classification experiments involving serum SERS spectra using\nartificial neural networks (ANNs) achieved a diagnostic sensitivity around 96% for differentiating AD\nsamples from HC samples in a binary model and 98% for differentiating AD, HC, and OD samples\nin a tertiary model. The results from this proof-of-concept study demonstrate the great potential of\nSERS blood serum analysis to be developed further into a novel clinical assay for the effective and\naccurate diagnosis of AD....
Since diabetes mellitus and osteoarthritis are highly prevalent diseases, combinations of\nantidiabetic agents like repaglinide (REP) and non-steroidal anti-inflammatory drugs (NSAID) like\ncelecoxib (CEL) could be commonly used in clinical practice. In this study, a simple and sensitive\nbioanalytical HPLC method combined with fluorescence detector (HPLC-FL) was developed and fully\nvalidated for simultaneous quantification of REP and CEL. A simple protein precipitation procedure\nand reversed C18 column with an isocratic mobile phase (mixture of ACN and pH 6.0 phosphate\nbuffer) were employed for sample preparation and chromatographic separation. The fluorescence\ndetector was set at a single excitation/emission wavelength pair of 240 nm/380 nm. The linearity\n(10â??2000 ng/mL), accuracy, precision, extraction recovery, matrix effect, and stability for this method\nwere validated as per the current FDA guidance. The bioanalytical method was applied to study\npharmacokinetic interactions between REP and CEL in vivo, successfully showing that concurrent\nadministration with oral REP significantly altered the pharmacokinetics of oral CEL. Furthermore, an\nin vitro metabolism and protein binding study using human materials highlighted the possibility of\nmetabolism-based interactions between CEL and REP in clinical settings....
Cachexia is a multifactorial wasting syndrome associated with high morbidity and mortality\nin patients with cancer. Diagnosis can be difficult and, in the clinical situation, usually relies upon\nreported weight loss. The â??omicsâ?? technologies allow us the opportunity to study the end points\nof many biological processes. Among these, blood-based metabolomics is a promising method to\ninvestigate the pathophysiology of human cancer cachexia and identify candidate biomarkers. In this\nstudy, we performed liquid chromatography mass spectrometry (LC/MS)-based metabolomics to\ninvestigate the metabolic profile of cancer-associated weight loss. Non-selected patients undergoing\nsurgery with curative intent for upper gastrointestinal cancer were recruited. Fasting plasma\nsamples were taken at induction of anaesthesia. LC/MS analysis showed that 6 metabolites were\nhighly discriminative of weight loss. Specifically, a combination profile of LysoPC 18.2, L-Proline,\nHexadecanoic acid, Octadecanoic acid, Phenylalanine and LysoPC 16:1 showed close correlation for\neight weight-losing samples ............................
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