Antibody Conjugated PLGA Nanocarriers and Superparmagnetic Nanoparticles for Targeted Delivery of Oxaliplatin to Cells from Colorectal Carcinoma

Anti-CD133 monoclonal antibody (Ab)-conjugated poly(lactide-co-glycolide) (PLGA) nanocarriers, for the targeted delivery of oxaliplatin (OXA) and superparamagnetic nanoparticles (IO-OA) to colorectal cancer cells (CaCo-2), were designed, synthesized, characterized, and evaluated in this study. The co-encapsulation of OXA and IO-OA was achieved in two types of polymeric carriers, namely, PLGA and poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) by double emulsion. PLGA_IO-OA_OXA and PEGylated PLGA_IO-OA_OXA nanoparticles displayed a comparable mean diameter of 207 ± 70 nm and 185 ± 119 nm, respectively. The concentration of the released OXA from the PEGylated PLGA_IO-OA_OXA increased very rapidly, reaching ~100% release after only 2 h, while the PLGA_IO-OA_OXA displayed a slower and sustained drug release. Therefore, for a controlled OXA release, non-PEGylated PLGA nanoparticles were more convenient. Interestingly, preservation of the superparamagnetic behavior of the IO-OA, without magnetic hysteresis all along the dissolution process, was observed. The non-PEGylated nanoparticles (PLGA_OXA, PLGA_IO-OA_OXA) were selected for the anti-CD133 Ab conjugation. The affinity of Ab-coated nanoparticles for CD133-positive cells was examined using fluorescence microscopy in CaCo-2 cells, which was followed by a viability assay.     

Modelling the production and degradation of soluble microbial products (SMP) in membrane bioreactors (MBR)

MBR biochemical conditions have an effect on membrane fouling and SMP have been attributed to be the main MBR foulant. Thus, predicting the SMP concentration is essential for understanding and controlling MBR fouling. However, existing SMP models are mostly too complex and over-parameterized, resulting in inadequate or absent parameter estimation and validation. This study extends the existing activated sludge model No. 2d (ASM2d) to ASM2dSMP with introduction of only 4 additional SMP-related parameters. Dynamic batch experimental results were used for SMP parameter estimation leading to reasonable parameter confidence intervals. Finally, the ASM2dSMP model was used to predict the impact of operational parameters on SMP concentration. It would found that solid retention time (SRT) is the key parameter controlling the SMP concentration. A lower SRT increased the utilization associated products (UAP) concentration, but decreased the biomass associated products (BAP) concentration and vice versa. A SRT resulting in minimum total SMP concentration can be predicted, and is found to be a relatively low value in the MBR. If MBRs operate under dynamic conditions and biological nutrient removal is required, a moderate SRT condition should be applied.     

Application of metal-free triazole formation in the synthesis of cyclic RGD-DTPA conjugates

The tandem 1,3-dipolar cycloaddition-retro-Diels-Alder (tandem crDA) reaction is presented as a versatile method for metal-free chemoselective conjugation of a DTPA radiolabel to N-delta-azido-cyclo(-Arg-Gly-Asp-d-Phe-Orn-) via oxanorbornadiene derivatives. To this end, the behavior of several trifluoromethyl-substituted oxanorbornadiene derivatives in the 1,3-dipolar cycloaddition was studied and optimized to give a clean and efficient method for bio-orthogonal ligation in an aqueous environment. After radioisotope treatment, the resulting 111In-labeled c(RGD)-CF3-triazole-DTPA conjugate was subjected to preliminary biological evaluation and showed high affinity for alpha(v)beta(3) (IC(50)=192 nM) and favorable pharmacokinetics.     

Intriguing Cytotoxicity of the Street Dissociative Anesthetic Methoxphenidine: Unexpected Impurities Spotted

The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate complex. Concerning the unknown and potentially hazardous properties of this sample, we performed an in vitro cytotoxicity screening in cell lines of various origins (e.g., kidney, liver, bladder) which was compared with the toxicity results of the methoxphenidine standard prepared for this purpose. The street methoxphenidine sample exhibited markedly higher toxicity than the standard, which was probably caused by the anion impurity. Since it is not usual to analyze anions in salts of novel psychoactive substances, but such samples may be commonly available at the drug black market, we have developed a method for their identification with X-ray powder diffraction (XRPD), which also enabled us to distinguish between different polymorphs/solvates of methoxphenidine that were crystallized in the laboratory. XRPD offers additional data about samples, which may not be discovered by routine techniques, and in some cases, they may help to find out essential information.     

Cognitive efficiency modes in old age: Performance on sequential and coordinative verbal and visuospatial tasks.

In an experiment using a large set of verbal and spatial tasks requiring low or high degrees of executive control, 3 distinct age-related effects were found. The smallest effect (no slowing was tied to lexical tasks with low executive involvement, the largest deficit (age-related slowing factor of 2.2) was tied to visuospatial tasks with high executive involvement, an intermediate level of deficit (slowing factor of 1.7) was found for visuospatial tasks with low executive load and verbal tasks with high executive load. These age-related dissociations were incompatible with any "common cause" formulation. The mechanism responsible for the dissociation between verbal and visual tasks, and between low and high executive load remains to be determined. The latter may reflect capacity limits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mammalian Cell Interaction with Periodic Surface Nanostructures

Here, we report on the nanopatterning of different aromatic polymer substrates achieved by KrF excimer laser treatment. The conditions for the construction of the laser-induced periodic surface structures, the so-called LIPSS pattern, were established by optimized laser fluence and a number of pulses. The polymer substrates were polyethylene naphthalate (PEN), polyethersulfone (PES), and polystyrene (PS), which were chosen since they are thermally, chemically, and mechanically resistant polymers with high absorption coefficients at the excimer laser wavelength. The surface morphology of the treated substrates was investigated by atomic force microscopy and scanning electron microscopy, and the roughness and effective surface area on the modified samples were determined. Elemental concentration was characterized by energy-dispersive (EDX) analysis, surface chemistry was determined with X-ray photoelectron spectroscopy (XPS). The samples with the formation of LIPSS induced by 10 mJ·cm⁻² with 1000, 3000, and 6000 pulses were used for subsequent in vitro cytocompatibility tests using human cells from osteosarcoma (U-2 OS). The LIPSS pattern and its ability of significant cell guidance were confirmed for some of the studied samples. Cell morphology, adhesion, and proliferation were evaluated. The results strongly contribute to the development of novel applications using nanopatterned polymers, e.g., in tissue engineering, cell analysis or in combination with metallization for sensor construction.     

Characterization of defects in titanium created by hydrogen charging

In the present work positron annihilation spectroscopy was employed for investigation of defects created in titanium by hydrogen loading. Pure titanium samples were firstly annealed to remove dislocations introduced by cutting and polishing. Subsequently the samples were loaded with hydrogen up to various hydrogen concentrations. Ti samples with different microstructures were compared: (i) conventional coarse grained sample, (ii) ultra fine grained material with microstructure refined by severe plastic deformation. Hydrogen gas loading of coarse grained and ultra fine grained samples was performed at hydrogen gas pressure of 103 bar and temperature of 150 °C. This resulted in formation of δ-TiH_x phase in Ti matrix. The hydrogen content absorbed in the samples was determined by thermogravimetric analysis. The phase composition of hydrogen-loaded samples was characterized by X-ray diffraction. Hydrogen loading introduced vacancies which agglomerated in the sample into small vacancy clusters. In addition to vacancies, dislocations were created by α-Ti → δ-TiH_x phase transition. Differential thermal analysis revealed that hydrogen is trapped at several kinds of traps characterized by different binding energies. The release of hydrogen from these traps precedes the decomposition of the δ-TiH_x phase.     

Plasma treated polyethylene grafted with adhesive molecules for enhanced adhesion and growth of fibroblasts

The cell–material interface plays a crucial role in the interaction of cells with synthetic materials for biomedical use. The application of plasma for tailoring polymer surfaces is of abiding interest and holds a great promise in biomedicine. In this paper, we describe polyethylene (PE) surface tuning by Ar plasma irradiating and subsequent grafting of the chemically active PE surface with adhesive proteins or motives to support cell attachment. These simple modifications resulted in changed polymer surface hydrophilicity, roughness and morphology, which we thoroughly characterized. The effect of our modifications on adhesion and growth was tested in vitro using mouse embryonic fibroblasts (NIH 3T3 cell line). We demonstrate that the plasma treatment of PE had a positive effect on the adhesion, spreading, homogeneity of distribution and moderately on proliferation activity of NIH 3T3 cells. This effect was even more pronounced on PE coated with biomolecules.     

Novel developments in the MOSFET dosemeter for neutron dosimetry applications

The feasibility of large-geometry Metal Oxide Semiconductor Field Effect Transistor (MOSFET) devices has been assessed for both active and passive neutron dosimetry and use in radiotherapy environments. Neutron sensitivity has been enhanced with the use of polymeric cement surrounding the gate region. Neutron activation via nuclear interaction processes is a potential problem with conventionally packaged and fabricated devices. To overcome this problem, a unique low-activation device design is described. Standard Dual in-Line devices, modified with polymeric cement and boron loaded cement have been exposed to gamma rays (60Co) and neutrons (gamma-ray shielded 252Cf) to provide neutron sensitivity estimates. The results show that the neutron sensitivity can be increased by a factor of approximately three by the use of a thin layer of polymeric cement over the gate region. Essentially zero activation is observed in the activation-reduced design compared with 1000 cps in the conventional design MOSFET when both are exposed under identical conditions to a neutron field from a gamma-ray shielded 252Cf isotopic source.