Controlled release of doxorubicin from the drug delivery formulation composed of single-walled carbon nanotubes and Congo red : a molecular dynamics study and dynamic light scattering analysis

The controlled delivery and release of drug molecules at specific targets increases the therapeutic efficacy of treatment. This paper presents a triple complex which is a new potential drug delivery system. Triple complex contains single-walled carbon nanotubes, Congo red, and doxorubicin. Nanotubes are built of a folded graphene layer providing a large surface for binding Congo red via “face-to-face” stacking which markedly increases the binding capacity of the carrier. Congo red is a compound that self-associates to form supramolecular ribbon-like structures, which are able to bind some drugs by intercalation. The nanotube–Congo red complex can bind the model drug doxorubicin. Thus, a new triple carrier system was obtained. The aim of this paper is to present studies on the controlled release of a model anticancer drug from a triple carrier system through pH changes. The specific aim of the study was to model the structure of the obtained experimental systems and to compare the changes in the average energy of interaction between its components induced by pH changes. The studies also aimed to compare the intensity of pH-dependent changes in hydrodynamic diameters of individual components of the triple carrier system. The effect of pH changes on the stability of the analyzed systems was examined using the molecular modeling method and dynamic light scattering. The decrease in pH influenced the structure and stability of the analyzed triple systems and ensured efficient drug release. The changes in hydrodynamic diameters of the obtained fractions were examined with the use of dynamic light scattering and were confirmed by computer simulation methods. The formulation presented in this paper shows potential for a therapeutic application owing to its high drug binding capacity and pH-dependent release. This ensures prolonged local action of the drug. The results reveal that the studied complex fulfills the basic requirements for its potential use as drug carrier, thus reducing side effects and enhancing pharmacological efficacy of drugs

New perspectives for undoped CaF2 scintillator as a threshold activation neutron detector

In this paper we present the prompt photofission neutron detection performance of undoped CaF2 scintillator using Threshold Activation Detection (TAD). The study is carried out in the frame of C-BORD Horizon 2020 project, during which an efficient toolbox for high volume freight non-intrusive inspection (NII) is under development. Technologies for radiation monitoring are the part of the project. Particularly, detection of various radiological threats on country borders plays an important significant role in Homeland Security applications. Detection of illegal transfer of Special Nuclear Material (SNM) - 235U, 233U and 239Pu - is particular due to the potential use for production of nuclear weapon as well as radiological dispersal device (RDD) V known also as a "dirty bomb". This technique relies on activation of 19F nuclei in the scintillator medium by fast neutrons and registration of high-energy β particles and γ-rays from the decay of reaction products. The radiation from SNM is detected after irradiation in order to avoid detector blinding. Despite the low 19F(n,α)16N or 19F(n,p)19O reaction cross-section, the method could be a good solution for detection of shielded nuclear material. Results obtained with the CaF2 detector were compared with the previous study done for BaF2 and 3He detector. These experimental results were obtained using 252Cf source and 9 MeV Varian Linatron M9 linear accelerator (LINAC). Finally, performance of the prompt neutron detection system based on CaF2 will be validated at Rotterdam Seaport during field trails in 2018

Applications of the variance orientation transform method to the multiscale characterization of surface roughness and anisotropy

There is no generally accepted method that could provide a full description of 3D surface topography (ST). Most of the currently used methods work well with isotropic surfaces at a single scale. Recently new method, called a variance orientation transform (VOT), has been developed for ST characterization. In this work, the usefulness of the VOT and its sensitivity to minute changes in ST have been tested. Images of real engineering surfaces, surfaces of adhesive wear particles and trabecular bone were used for the tests. The results obtained show that the VOT can be useful in both engineering and medical applications

Stability and Existence of Noncanonical I-motif DNA Structures in Computer Simulations Based on Atomistic and Coarse-Grained Force Fields

Cytosine-rich DNA sequences are able to fold into noncanonical structures, in which semi-protonated cytosine pairs develop extra hydrogen bonds, and these bonds are responsible for the overall stability of a structure called the i-motif. The i-motif can be formed in many regions of the genome, but the most representative is the telomeric region in which the CCCTAA sequences are repeated thousands of times. The ability to reverse folding/unfolding in response to pH change makes the above sequence and i-motif very promising components of nanomachines, extended DNA structures, and drug carriers. Molecular dynamics analysis of such structures is highly beneficial due to direct insights into the microscopic structure of the considered systems. We show that Amber force fields for DNA predict the stability of the i-motif over a long timescale; however, these force fields are not able to predict folding of the cytosine-rich sequences into the i-motif. The reason is the kinetic partitioning of the folding process, which makes the transitions between various intermediates too time-consuming in atomistic force field representation. Application of coarse-grained force fields usually highly accelerates complex structural transitions. We, however, found that three of the most popular coarse-grained force fields for DNA (oxDNA, 3SPN, and Martini) were not able to predict the stability of the i-motif structure. Obviously, they were not able to accelerate the folding of unfolded states into an i-motif. This observation must be strongly highlighted, and the need to develop suitable extensions of coarse-grained force fields for DNA is pointed out. However, it will take a great deal of effort to successfully solve these problems

Analysis of AFM images of self-structured surface textures by directional fractal signature method

A new method, called augmented blanket with rotating grid (ABRG), has been proposed in our recent work on characterizing roughness and directionality of self-structured surface textures. This is the first method that calculates fractal dimensions (FDs) at individual scales and directions for the entire surface image data and does not require the data to be Brownian fractal. However, before the ABRG method can be used in real applications, effects of atomic force microscope (AFM) imaging conditions on FDs need to be evaluated first. In this paper, computer-generated AFM images with three different resolutions, 48 combinations of tip radii and cone angles, and 15 noise levels were used in the tests. The images represent isotropic self-structured surface textures with small, medium and large motif sizes, and anisotropic surfaces exhibiting two dominating directions. For isotropic surfaces, the ABRG method is not significantly affected (i.e. FDs changes <5 %) by image resolution, tip size (for surfaces with large motifs) and noise (except the level above 8 %). For anisotropic surfaces, the method exhibits large changes in FDs (up to −34 %). The results obtained show that the ABRG method can be effective in analysing the AFM images of self-structured surface textures. However, some precautions should be taken with anisotropic and isotropic surfaces with small motifs

A new method to measure trabecular bone texture on hand radiographs: data from the osteoarthritis initiative

Purpose: Grading of hand radiographs for joint space narrowing and osteophytes is the traditional method for assessing hand OA. However this assessment can be difficult and inaccurate since the changes of cartilage volume in finger joints are small the grading requires experienced readers to be reproducible and there is no sensitivity to early OA. Thus a new hand OA assessment method is required. A solution could be in the applications of fractal analyses of finger bone texture regions selected on hand radiographs. The reasons are that the bone texture changes in early stages of OA it exhibits fractal nature and it is related to 3D bone structure. However currently there is no method that could quantify accurately small size bone regions on hand radiographs. We have developed a new method called augmented variance orientation transform (AVOT) method to measure the roughness and directionality of small texture regions at individual scales. Methods: The AVOT method calculates the fractal signatures (FSs) in different directions. FS is a set of fractal dimensions (FDs) calculated at individual image sizes (i.e. scales) while FD is a measure of texture roughness. High value of FD means a rougher texture. The method allows for the analysis of hand bone texture regions that are small in size and selected on arbitrarily oriented fingers.Initially we evaluated whether our method can accurately differentiate between computer generated isotropic and anisotropic fractal texture images of sizes ranging from 20 × 20 to 64 × 64 pixels. This is because roughness and anisotropy of bone texture changes with OA. These sizes correspond to those found on hand radiographs. Isotropic textures had FDs varying from 2.1 to 2.9 in steps of 0.1 (400 images per FD) while anisotropic textures had dominating directions of 120° and 30° (400 images per direction).For those images three parameters at scales ranging from 2 to 7 pixels (depending on image size) were calculated i.e. FS along the direction of the texture roughest part (FSSta) aspect ratio (StrS) and direction signatures (StdS) respectively. The aspect ratio and direction measure the texture anisotropy. We also evaluated our method for its sensitivity in differentiating the bone texture between subjects with and without radiographic hand OA. The subjects were taken from the Osteoarthritis Initiative (OAI) public use data set (OAI Datasets 0.2.2 and 0.C.1). Images from centre A were used since they exhibit smallest size amongst the five centres (150 DPI). This strategy allows for testing “the worst scenario” i.e. 20 × 20 pixel regions. We used 20 pairs of subjects (n = 20 14 women) with (OA cases) and without (controls) OA in the 5th distal interphalangeal (DIP5) joint. OA was defined as: (i) joint space narrowing (JSN) grade 2 or worse (ii) osteophyte grade 2 or worse or (iii) JSN grade 1 with an osteophyte grade 1. These criteria approximate Kellgren and Lawrence (K/L) grade 2 or worse. The case-control pairs were individually matched by sex age body mass index and race. For each hand x-ray 20 × 20 pixels bone texture regions were selected on the distal and middle phalanges adjacent to the DIP5 joint (Figure 1). For each bone region the FSSta StrS StdS parameters were calculated at scales of 0.34 and 0.51 mm. One-way analysis of variance ANOVA with Tuckey HSD (Games-Howell if appropriate) post hoc tests and paired samples t-tests (Wilcoxon signed-rank tests if appropriate) were used (p < 0.05 is significant).Results: For all image sizes and scales values of FSSta were statistically significantly different between isotropic fractal images. StrS values obtained for anisotropic surfaces were lower than those for isotropic surfaces and StdS agreed with the dominating directions. Compared to the controls OA middle phalanges exhibited significantly lower FSSta at sizes 0.34 and (p = 0.018) and 0.51 mm (p = 0.021) and higher StrS at 0.34 (p = 0.015) and 0.51 mm (p = 0.002). In the distal phalanx FSSta at size of 0.34 mm (p = 0.044) was lower for OA cases than controls. Conclusions: The AVOT method can differentiate between small isotropic and anisotropic fractal textures and also between finger bones with and without radiographic OA. Although further large-scale studies are still required our results show the potential of the method for the quantification of OA changes in the finger bone structure

Cytosine-Rich DNA Fragments Covalently Bound to Carbon Nanotube as Factors Triggering Doxorubicin Release at Acidic pH. A Molecular Dynamics Study

This works deals with analysis of properties of a carbon nanotube, the tips of which were functionalized by short cytosine-rich fragments of ssDNA. That object is aimed to work as a platform for storage and controlled release of doxorubicin in response to pH changes. We found that at neutral pH, doxorubicin molecules can be intercalated between the ssDNA fragments, and formation of such knots can effectively block other doxorubicin molecules, encapsulated in the nanotube interior, against release to the bulk. Because at the neutral pH, the ssDNA fragments are in form of random coils, the intercalation of doxorubicin is strong. At acidic pH, the ssDNA fragments undergo folding into i-motifs, and this leads to significant reduction of the interaction strength between doxorubicin and other components of the system. Thus, the drug molecules can be released to the bulk at acidic pH. The above conclusions concerning the storage/release mechanism of doxorubicin were drawn from the observation of molecular dynamics trajectories of the systems as well as from analysis of various components of pair interaction energies

Characterization of Surface Topography from Small Images

Detailed characterization of 3D engineering surface topographies is still an unresolved problem. The reasons are that the majority of the real surfaces are anisotropic and multi-scale, i.e. their directionality and roughness change with the measurement scales. To solve this problem, a variance orientation transform (VOT) method was developed. It calculates fractal dimensions at individual scales, i.e. it calculates the fractal signature (FS) in all possible directions, addressing, in this way, the problems of surfaces' multi-scale and anisotropic nature. However, the VOT method is not suited for the analysis of image sizes that are smaller than 48 × 48 pixels (e.g. images of wear particles surfaces, small surface defects, etc.). To redress this problem the VOT method was augmented so that it can calculate FSs for all images including those with small sizes. Previous study showed that the augmented VOT (AVOT) method is accurate in the analysis of hand x-ray images where the bone texture images are small (20 × 20 pixels). However, its usefulness in analysing small images of engineering surfaces has not yet been investigated. In the current study, we use range-images of different sizes (20 × 20 and 30 × 30 pixels) of polished (isotropic) and ground (anisotropic) steel plates. When applied to images of steel surfaces of different topography, the AVOT method has detected minute changes at different scales, undetectable by other commonly used surface characterization methods, between the surfaces. The results show that the method can be a valuable tool in characterization of small images of 3D engineering surfaces

Effects of information loss in texture details due to the PIFS encoding on load and friction in hydrodynamic bearings

Textured surfaces can significantly improve the performance of hydrodynamic bearings. However, there is no generally accepted method for their accurate and automated 3D characterization. A promising solution to this problem is partition iterated function system (PIFS) model, which encapsulates information about 3D topography of textured surfaces. However, some loss in surface details can occur. Therefore, before PIFS could be used, effects of this information loss on load and friction need to be investigated. In this study, this issue was addressed using a textured hydrodynamic pad bearing. The results obtained showed that PIFS models might become useful in characterization of textured surfaces