Promising gene delivery system based on polyethylenimine-modified silica nanoparticles.

This article reports on the synthesis and full characterization of innovative silica-based nanoparticle composed of fumed silica as a core decorated with polyethylenimine (PEI) with different molecular weights (25, 10 and 1.8 kDa). Wide range of analytical, spectroscopic, and microscopic methods (TEM, DLS, ζ potential, elemental analysis (EA), TNBS and FTIR) were used to characterize the nanoparticles. Furthermore, transfection efficiency of these nanoparticles as non-viral vector was examined. The silica-PEI conjugates retained both the ability of PEI to fully condense plasmid DNA at low N/P ratios and suitable buffering capacity at the endosomal pH range. PEI-functionalized silica remarkably enhanced EGFP-N1 gene expression in murine neuroblastoma (Neuro-2A) cells up to 38 folds compared to PEI 25 kDa. Meanwhile the results of the cytotoxicity assays indicated that these silica-PEI conjugates have acceptable level of viability.

A fluorescent aptasensor for potassium ion detection-based triple-helix molecular switch.

Here, a biosensor based on a quadruplex-forming aptamer for the determination of potassium ion (K(+)) is presented. The aptamer was used as a molecular recognition element; it was adjacent to two arm fragments and a dual-labeled oligonucleotide serving as a signal transduction probe (STP) that is complementary of the arm fragment sequence. In the presence of K(+), the aptamer was displaced from the STP, which was accompanied by decreased signal. The quenching percentage of fluorescence intensity was proportional to the concentration of K(+) in the range of 0.05 to 1.4mM. A detection limit of 0.014 mM was achieved. Furthermore, other metal ions, such as Na(+), Li(+), NH4(+), Mg(2+), and Ca(2+), caused no notable interference on the detection of K(+).

Antinociceptive evaluation of ceftriaxone and minocycline alone and in combination in a neuropathic pain model in rat.

Glutamate homeostasis and microglia activation play an important role in the development and maintenance of neuropathic pain. So far, there has been insufficient data on the relationship between glutamate transporters and cytokines in neuropathic pain. This investigation was designed to evaluate the interaction between co-administration of ceftriaxone, a specific GLT1 activator and minocycline, a specific microglia inhibitor, on the mechanical and cold allodynia of chronic constriction injury model (CCI) in rats. Moreover, alteration of the spinal concentration of proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) was studied. Ceftriaxone (100, 150 and 200mg/kg, i.p.) and minocycline (25, 50 and 100mg/kg, i.p.) were administered either alone or in combination for 7 days. Gabapentin (100mg/kg, i.p.) was selected as a reference drug. Behavioral evaluations were performed 1 day before and on days 3, 5, 7, 10 and 14 after surgery. Each of drugs produced a dose-dependent reversal of the neuropathic pain behaviors. Area under the curve (AUC) of combination therapy revealed that minocycline potentiated cold and mechanical antiallodynic effects of ceftriaxone. TNF-α and IL-1ß increased in the spinal cord of CCI animals on days 3, 7 and 14 post-surgery. Production of studied cytokines was significantly attenuated after treatment with ceftriaxone alone and in combination with minocycline compared with control group. It is suggested that combination of these classes of drugs would be a promising approach for treatment of chronic neuropathic pain.