The production and abuse of new psychoactive substances, known as "legal highs" which mimic traditional drugs of abuse is becoming a global epidemic. Traditional analytical methodologies exist which can provide confirmatory analysis but there is a requirement for an on-the-spot analytical screening tool that could be used to determine whether a substance, or sample matrix contains such legal, or formally "legal highs". In this paper the electrochemical sensing of (±)-methcathinone and related compounds at a range of commercially available electrode substrates is explored. We demonstrate for the first time that this class of "legal highs" are electrochemically active providing a novel sensing protocol based upon their electrochemical oxidation. Screen-printed graphite sensing platforms are favoured due to their proven ability to be mass-produced providing large numbers of reliable and reproducible electrode sensing platforms that preclude the requirement of surface pre-treatment such as mechanical polishing as is the case in the use of solid/re-usable electrode substrates. Additionally they hold potential to be used on-site potentially being the basis of an on-site legal high screening device. Consequently the electroanalytical sensing of (±)-methcathinone (3a), (±)-4′-methylmethcathinone [3b, 4-MMC, (±)-mephedrone] and (±)-4′-methyl-N-ethylcathinone (3c, 4-MEC) is explored using screen-printed sensing platforms with the effect of pH explored upon the analytical response with their analytical efficiency evaluated towards the target legal highs. Interesting at pH values below 6 the voltammetric response quantitatively changes from that of an electrochemically irreversible response to that of a quasi-reversible signature which can be used analytically. It is demonstrated for the first time that the electroanalytical sensing of (±)-methcathinone (3a), (±)-mephedrone (3b) and 4-MEC (3c) are possible with accessible linear ranges found to correspond to 16–200 μg mL(−1) for 3a (at pH 12) and 16–350 μg mL(−1) for both 3b and 3c in pH 2, with limits of detection (3σ) found to correspond to 44.5, 39.8 and 84.2 μg mL(−1) respectively. Additionally adulterants that are commonly incorporated into cathinone legal highs are electrochemically explored at both pH 2 and 12.
Diaminobutyric polypropylenimine (DAB) dendrimers have been shown to be highly efficient non-viral gene delivery systems for cancer therapy. However, their cytotoxicity currently limits their applications. To overcome this issue, PEGylation of DAB dendrimer, using various PEG molecular weights and dendrimer generations, has been attempted to decrease the cytotoxicity and enhance the DNA condensation, size and zeta potential, cellular uptake and transfection efficacy of these dendriplexes. Among all the PEGylated dendrimers synthesized, generation 3- and generation 4-DAB conjugated to low molecular weight PEG (2 kDa) at a dendrimer: DNA ratio of 20:1 and 10:1 resulted in an increase in gene expression on almost all tested cancer cells lines (by up to 3.2-fold compared to unmodified dendrimer in A431 cells). The highest level of β-galactosidase gene expression (10.07 × 10−3 ± 0.09 × 10−3 U/mL) was obtained following treatment of B16F10-Luc cells with G4-dendrimer PEGylated with PEG2K at a dendrimer: DNA ratio of 20:1. These delivery systems significantly decreased cytotoxicity on B16F10-Luc cells, by more than 3.4-fold compared to unmodified dendrimer. PEGylated generations 3- and 4-DAB dendrimers are therefore promising gene delivery systems for cancer therapy, combining low cytotoxicity and high transfection efficacy.
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