Evaluation of the functionality of biodegradable polymeric platforms for drug delivery systems

We present the development of a drug-loaded triple-layer platform consisting of thin film biodegradable polymers, in a properly designed form for the desired gradual degradation. Poly(dl-lactide-co-glycolide) (PLGA (65:35), PLGA (75:25)) and polycaprolactone (PCL) were grown by spin coating technique, to synthesize the platforms with the order PCL/PLGA (75:25)/PLGA (65:35) that determine their degradation rates. The outer PLGA (65:35) layer was loaded with dipyridamole, an antiplatelet drug. Spectroscopic ellipsometry (SE) in the Vis-far UV range was used to determine the nanostructure, as well as the content of the incorporated drug in the as-grown platforms. In situ and real-time SE measurements were carried out using a liquid cell for the dynamic evaluation of the fibrinogen and albumin protein adsorption processes. Atomic force microscopy studies justified the SE results concerning the nanopores formation in the polymeric platforms, and the dominant adsorption mechanisms of the proteins, which were defined by the drug incorporation in the platforms. © 2013 Elsevier B.V. All rights reserved.

Androgen receptor targets NFKB and TSPI to suppress prostate tumor growth in vivo

The androgen role in the maintenance of prostate epithelium is subject to conflicting opinions. While androgen ablation drives the regression of normal and cancerous prostate, testosterone may cause both proliferation and apoptosis. Several investigators note decreased proliferation and stronger response to chemotherapy of the prostate cancer cells stably expressing androgen receptor (AR), however no mechanistic explanation was offered. In this paper we demonstrate in vivo anti-tumor effect of the AR on prostate cancer growth and identify its molecular mediators. We analyzed the effect of AR on the tumorigenicity of prostate cancer cells. Unexpectedly, the AR-expressing cells formed tumors in male mice at a much lower rate than the AR-negative controls. Moreover, the AR-expressing tumors showed decreased vascularity and massive apoptosis. AR expression lowered the angiogenic potential of cancer cells, by increasing secretion of an anti-angiogenic protein, thrombospondin-1. AR activation caused a decrease in RelA, a subunit of the pro-survival transcription factor NF kappa B, reduced its nuclear localization and transcriptional activity. This, in turn, diminished the expression of its anti-apoptotic targets, Bcl-2 and IL-6. Increased apoptosis within AR-expressing tumors was likely due to the NF kappa B suppression, since it was restricted to the cells lacking nuclear (active) NF kappa B. Thus we for the first time identified combined decrease of NF kappa B and increased TSP1 as molecular events underlying the AR anti-tumor activity in vivo. Our data indicate that intermittent androgen ablation is preferable to continuous withdrawal, a standard treatment for early-stage prostate cancer. (C) 2007 Wiley-Liss, Inc.

Feasibility study of carbon nanotube microneedles for rapid transdermal drug delivery

We introduce a new approach for fabricating hollow microneedles using vertically-aligned carbon nanotubes (VA-CNTs) for rapid transdermal drug delivery. Here, we discuss the fabrication of the microneedles emphasizing the overall simplicity and flexibility of the method to allow for potential industrial application. By capitalizing on the nanoporosity of the CNT bundles, uncured polymer can be wicked into the needles ultimately creating a high strength composite of aligned nanotubes and polymer. Flow through the microneedles as well as in vitro penetration of the microneedles into swine skin is demonstrated. Furthermore, we present a trade study comparing the difficulty and complexity of the fabrication process of our CNT-polymer microneedles with other standard microneedle fabrication approaches. Copyright © Materials Research Society 2013.

Retention of the developmental pluripotency in medaka embryonic stem cells after gene transfer and long-term drug selection for gene targeting in fish

Embryonic stem (ES) cells provide a unique tool for introducing random or targeted genetic alterations, because it is possible that the desired, but extremely rare recombinant genotypes can be screened by drug selection. ES cell-mediated transgenesis has so far been limited to the mouse. In the fish medaka (Oryzias latipes) several ES cell lines have been made available. Here we report the optimized conditions for gene transfer and drug selection in the medaka ES cell line MES1 as a prelude for gene targeting in fish. MES1 cells gave rise to a moderate to high transfection efficiency by the calcium phosphate co-precipitation (5%), commercial reagents Fugene (11%), GeneJuice (21%) and electroporation (>30%). Transient gene transfer and CAT reporter assay revealed that several enhancers/promoters and their combinations including CMV, RSV and ST (the SV40 virus early gene enhancer linked to the thymidine kinase promoter) were suitable regulatory sequences to drive transgene expression in the MES1 cells. We show that neo, hyg or pac conferred resistance to G418, hygromycin or puromycin for positive selection, while the HSV-tk generated sensitivity to ganciclovir for negative selection. The positive-negative selection procedure that is widely used for gene targeting in mouse ES cells was found to be effective also in MES1 cells. Importantly, we demonstrate that MES1 cells after gene transfer and long-term drug selection retained the developmental pluripotency, as they were able to undergo induced differentiation in vitro and to contribute to various tissues and organs during chimeric embryogenesis.

The preparation of 238U targets on 2mm Al foils

Preparation of 238U on 2μm Al foils by molecular plating technique is described. In order to obtain optimum conditions for deposition, several parameters influencing the quality of layers such as current density, distance between the anode and cathode and the deposition time were investigated. The target thickness was determined by spectrophotometry. The uniformity and morphology of the target surface were studied by means of scanning electron microscopy, energy dispersive X-ray spectrometry and Infrared spectra. The results show that uranium is deposited in its oxide or hydroxide form uniformly and adherently onto the foil.

Production of new superheavy Z=108-114 nuclei with U-238, Pu-244, and Cm-248,Cm-250 targets

Within the framework of the dinuclear system (DNS) model, production cross sections of new superheavy nuclei with charged numbers Z=108-114 are analyzed systematically. Possible combinations based on the actinide nuclides U-238, Pu-244, and Cm-248,Cm-250 with the optimal excitation energies and evaporation channels are pointed out to synthesize new isotopes that lie between the nuclides produced in the cold fusion reactions and the Ca-48-induced fusion reactions experimentally, which are feasible to be constructed experimentally. It is found that the production cross sections of superheavy nuclei decrease drastically with the charged numbers of compound nuclei. Larger mass asymmetries of the entrance channels enhance the cross sections in 2n-5n channels.