Doxorubicin-loaded cholic acid-polyethyleneimine micelles for targeted delivery of antitumor drugs: synthesis,characterization, and evaluation of their in vitro cytotoxicity

Doxorubicin-loaded micelles were prepared from a copolymer comprising cholic acid (CA) and polyethyleneimine (PEI) for the delivery of antitumor drugs. The CA-PEI copolymer was synthesized via pairing mediated by N,N’-dicyclohexylcarbodiimide and N-hydroxysuccinimide using dichloromethane as a solvent. Fourier transform infrared and nuclear magnetic resonance analyses were performed to verify the formation of an amide linkage between CA and PEI and doxorubicin localization into the copolymer. Dynamic light scattering and transmission electron microscopy studies revealed that the copolymer could self-assemble into micelles with a spherical morphology and an average diameter of <200 nm. The CA-PEI copolymer was also characterized by X-ray diffraction and differential scanning calorimetry. Doxorubicin-loaded micelles were prepared by dialysis method. A drug release study showed reduced drug release with escalating drug content. In a cytotoxicity assay using human colorectal adenocarcinoma (DLD-1) cells, the doxorubicin-loaded CA-PEI micelles exhibited better antitumor activity than that shown by doxorubicin. This is the first study on CA-PEI micelles as doxorubicin carriers, and this study demonstrated that they are promising candidates as carriers for sustained targeted antitumor drug delivery system.     

Characterization of Al2O3 thin films fabricated through atomic layer deposition on polymeric substrates

This paper reports on the fabrication of good quality Al₂O₃ thin films on flexible substrates including polyethylene naphthalate (PEN), polyethylene terephthalate (PET) and Polyamide at different temperatures down to 50 °C under very short water purging steps of 10 s. Al₂O₃ films with appreciable growth rates having good morphological, chemical, electrical and optical characteristics have been produced. Growth rates of 1.16, 1.14 and 1.15 Å/cycle have been observed at 50 °C for PET, PEN and polyamide substrates respectively. The surface morphology has been improved with the increase in deposition temperature. Low average arithmetic roughness of 0.88 and 0.78 nm have been recorded for the Al₂O₃ films deposited at 150 °C on PEN and polyamide respectively. The XPS analysis confirmed the fabrication of Al₂O₃ films without any carbon contamination and Al 2p, Al 2s and O 1s peaks were appeared at binding energies of 74, 119 and 531 eV, respectively. Excellent insulating properties were observed for the Al₂O₃ films and optical transmittance of more than 85 % was recorded in the visible region. The experimental results suggest that polymeric materials are excellent candidates to be used as substrates in the fabrication of Al₂O₃ thin films through atomic layer deposition.     

Coupled heat conduction and thermal stress analyses in particulate composites

This study introduces two micromechanical modeling approaches to analyze spatial variations of temperatures, stresses and displacements in particulate composites during transient heat conduction. In the first approach, a simple micromechanical model based on a first order homogenization scheme is adopted to obtain effective mechanical and thermal properties, i.e., coefficient of linear thermal expansion, thermal conductivity, and elastic constants, of a particulate composite. These effective properties are evaluated at each material (integration) point in three dimensional (3D) finite element (FE) models that represent homogenized composite media. The second approach treats a heterogeneous composite explicitly. Heterogeneous composites that consist of solid spherical particles randomly distributed in homogeneous matrix are generated using 3D continuum elements in an FE framework. For each volume fraction (VF) of particles, the FE models of heterogeneous composites with different particle sizes and arrangements are generated such that these models represent realistic volume elements “cut out” from a particulate composite. An extended definition of a RVE for heterogeneous composite is introduced, i.e., the number of heterogeneities in a fixed volume that yield the same expected effective response for the quantity of interest when subjected to similar loading and boundary conditions. Thermal and mechanical properties of both particle and matrix constituents are temperature dependent. The effects of particle distributions and sizes on the variations of temperature, stress and displacement fields are examined. The predictions of field variables from the homogenized micromechanical model are compared with those of the heterogeneous composites. Both displacement and temperature fields are found to be in good agreement. The micromechanical model that provides homogenized responses gives average values of the field variables. Thus, it cannot capture the discontinuities of the thermal stresses at the particle-matrix interface regions and local variations of the field variables within particle and matrix regions.     

Intergranular corrosion behavior of the 7075-T6 aluminum alloy under different annealing conditions

The effect of annealing conditions producing various grain sizes on the intergranular corrosion behavior of high-strength aluminum alloy type 7075-T6 was investigated using electrochemical polarization techniques. Aluminum alloy specimens with large grain size exhibited lower breakdown potentials in deaerated 0.5 M NaCl solution. The breakdown potentials decreased with increasing grain size. Microscopic observations of the exposed surfaces during potentiostatic polarization testing showed that the coarse grain structure promotes intergranular crack growth.     

Second-order effects at microindentation of elastic polymers using sharp indenters

Sharp indentation of elastic polymers is investigated numerically using the finite element method. Large deformation theory is relied upon for accuracy. Both cone and Vickers indentation is considered and in particular, the study focuses on second-order effects on relevant indentation quantities in the microindentation regime. The second-order effects include indenter tip roundness, friction and also, for generality, effects due to different values on the included angle of the cone indenter, α. It is shown that frictional effects as well as effects due to indenter tip roundness are small at cone indentation but friction can substantially influence the results in case of Vickers indentation. The latter feature is most likely due to frictional effects at the ridges of the indenter and as such behavior is not accurately described using conventional theory of friction, a numerical approach for this purpose is discussed.     

Elastic solution of a two-dimensional functionally graded thick truncated cone with finite length under hydrostatic combined loads

In this paper, a thick truncated hollow cone with finite length made of two-dimensional functionally graded materials (2D-FGM) subjected to combined loads as internal, external and axial pressure is considered. The volume fraction distribution of materials and geometry are assumed to be axisymmetric but not uniform along the axial direction. The Finite Element Method based on the Rayliegh-Ritz energy formulation is applied to obtain the elastic behavior of the functionally graded thick truncated cone. By using this method, the effects of semi-vertex angle of the cone and the power law exponents on the distribution of different types of displacements and stresses are considered. The results show that using 2D-FGM leads to a more flexible design so that both the maximum stresses and stress distribution can be controlled by the material distribution.     

Modeling of failure mode of laser welds in lap-shear specimens of HSLA steel sheets

Failure mode of laser welds in lap-shear specimens of high strength low alloy (HSLA) steel sheets is investigated in this paper. The experiments for laser welds in lap-shear specimens under quasi-static loading conditions are briefly reviewed first. The experimental results showed that the laser welds failed in a ductile necking/shear failure mode and the ductile failure was initiated at a distance away from the crack tip near the boundary of the base metal and heat affected zone. In order to understand the failure mode of these welds, finite element analyses under plane strain conditions were conducted to identify the effects of the different plastic behaviors of the base metal, heat affected zone, and weld zone as well as the weld geometry on the ductile failure. The results of the reference finite element analysis based on the homogenous material model show that the failure mode is most likely to be a middle surface shear failure mode in the weld. The results of the finite element analysis based on the multi-zone non-homogeneous material models show that the higher effective stress–plastic strain curves of the weld and heat affected zones and the geometry of the weld protrusion result in the necking/shear failure mode in the load carrying sheet. The results of another finite element analysis based on the non-homogeneous material model and the Gurson yield function for porous materials indicate that the consideration of void nucleation and growth is necessary to identify the ductile failure initiation site that matches well with the experimental observations. Finally, the results of this investigation indicate that the failure mode of the welds should be examined carefully and the necking/shear failure mode needs to be considered for development of failure or separation criteria for welds under more complex loading conditions.     

The S-transform using a new window to improve frequency and time resolutions

The S-transform presents arbitrary time series as localized invertible time–frequency spectra. This transformation improves the short-time Fourier transform and the wavelet transform by merging the multiresolution and frequency-dependent analysis properties of wavelet transform with the absolute phase retaining of Fourier transform. The generalized S-transform utilizes a combination of a Fourier transform kernel and a scalable-sliding window. The common S-transform applies a Gaussian window to provide appropriate time and frequency resolution and minimizes the product of these resolutions. However, the Gaussian S-transform is unable to obtain uniform time and frequency resolution for all frequency components. In this paper, a novel window based on the $t$ student distribution is proposed for the S-transform to achieve a more uniform resolution. Simulation results show that the S-transform with the proposed window provides in comparison with the Gaussian window a more uniform resolution for the entire time and frequency range. The result is suitable for applications such as spectrum sensing.