Magnetic nanoparticle formulations for DNA and siRNA delivery

Newly synthesized magnetic nanomaterials possess high DNA binding capacity either itself or in the presence of a positively charged lipid-based Metafectene™ reagent or branched polyethylene imine 25 kDa. Polyethylene imine (PEI)-modified nanomaterials are able to deliver nucleic acids in cell culture in duplexes. Magnetofection with triplexes of nanomaterials results in higher transduction efficiencies compared to optimal PEI or Metafectene formulations. 90% transient down-regulation of the target protein in HeLa-green fluorescence protein cells was achieved at short interfering RNA concentrations as low as 8 nM with a formulation of PEI-modified nanoparticles.     

The inhibitory potential of Thai mango seed kernel extract against methicillin-resistant Staphylococcus aureus

Plant extracts are a valuable source of novel antibacterial compounds to combat pathogenic isolates of methicillin-resistant Staphylococcus aureus (MRSA), a global nosocomial infection. In this study, the alcoholic extract from Thai mango (Mangifera indica L. cv. 'Fahlun') seed kernel extract (MSKE) and its phenolic principles (gallic acid, methyl gallate and pentagalloylglucopyranose) demonstrated potent in vitro antibacterial activity against Staphylococcus aureus and 19 clinical MRSA isolates in studies of disc diffusion, broth microdilution and time-kill assays. Electron microscopy studies using scanning electron microscopy and transmission electron microscopy revealed impaired cell division and ultra-structural changes in bacterial cell morphology, including the thickening of cell walls, of microorganisms treated with MSKE; these damaging effects were increased with increasing concentrations of MSKE. MSKE and its phenolic principles enhanced and intensified the antibacterial activity of penicillin G against 19 clinical MRSA isolates by lowering the minimum inhibitory concentration by at least 5-fold. The major phenolic principle, pentagalloylglucopyranose, was demonstrated to be the major contributor to the antibacterial activity of MSKE. These results suggest that MSKE may potentially be useful as an alternative therapeutic agent or an adjunctive therapy along with penicillin G in the treatment of MRSA infections.     

In vitro pH-dependent drug release from N4-(4-carboxybutyryl)-1-beta-D-arabinofuranosylcytosine and its conjugate with poly-L-lysine or decylenediamine-dextran T70

N4-(4-Carboxybutyryl)-1-beta-D-arabinofuranosylcytosine (glu-ara-C), the conjugate of glu-ara-C and poly-L-lysine (PLL), (PLL-glu-ara-C), and the conjugate of glu-ara-C and decylenediamine-dextran T70 (T70-C10), (T70-C10-glu-ara-C), were prepared. Drug regeneration from glu-ara-C and the conjugates was investigated in buffered solutions of pH 4,5,7,7.4 and 8. The character of the drug release from the conjugates was different from that from glu-ara-C. Namely, the release of 1-beta-D-arabinofuranosylcytosine (ara-C) from glu-ara-C was accelerated under both weakly acidic and weakly basic conditions, while it was accelerated only under weakly basic conditions from the conjugates. Overall, the drug release profiles from the conjugates showed similar patterns. However, under neutral and weakly basic conditions, ara-C was regenerated more rapidly from PLL-glu-ara-C than from T70-C10-glu-ara-C. During the incubation of glu-ara-C and the conjugates under weakly acidic conditions, 1-beta-D-arabinofuranosyluracil (ara-U) was detected and its amount increased with time to similar extents.