Monolayer System Research Articles

Understanding the Interplay Between Uptake and Efflux Transporters Within In Vitro Systems in Defining Hepatocellular Drug Concentrations

One of the most holistic in vitro systems for prediction of intracellular drug concentrations is sandwich-cultured hepatocytes (SCH); however, a comprehensive evaluation of the utility of SCH to estimate uptake and biliary clearances and the need for additional kinetic parameters has yet to be carried out. Toward this end, we have selected 9 compounds (rosuvastatin, valsartan, fexofenadine, pravastatin, repaglinide, telmisartan, atorvastatin, saquinavir, and quinidine) to provide a range of physicochemical and hepatic disposition properties. Uptake clearances were determined in SCH and compared with conventional monolayer and suspension hepatocyte systems, previously reported by our laboratory. CLuptake ranged from 1 to 41 μL/min/106 cells in SCH which were significantly lower (1%-10%) compared with the other hepatocyte models. The hepatocyte-to-media unbound concentration ratio (Kpu) has been assessed and ranged 0.7-59, lower compared with other hepatocyte systems (8-280). Estimates of in vitro biliary clearance (CLbile) for 4 drugs were determined and were scaled to predict in vivo values using both intracellular concentration and media drug concentrations. These studies demonstrate that reduced uptake in rat SCH may limit drug access to canalicular efflux transport proteins and highlight the importance of elucidating the interplay between these proteins for accurate prediction of hepatic clearance.

Light absorption by ordered planar structure of crystalline silicon particles: Simulation as applied to enhancement of the solar cell performance

Light absorption by a single spherical crystalline silicon (c-Si) particle and by monolayers of submicron c-Si particles arranged in triangular lattice is examined within the wavelength range from 0.28 to 1.12 μm. Data for spectral and integrated (over the terrestrial solar spectral irradiance “Global tilt” ASTM G173-03) absorption coefficients of monolayer demonstrating the possibility to enhance light absorption by a particulate active layer of crystalline silicon are presented. They are calculated in the quasicrystalline approximation of the theory of multiple scattering of waves. It is shown that in the narrow wavelength intervals (up to 10 nm) the spectral absorption coefficient of monolayer can be more than 100 times larger than the one of the plane-parallel plate of equal volume of material. Some results on the transmittance and reflectance of partially ordered monolayer are presented as well. The potentialities of light absorption enhancement in a single monolayer and three-monolayer system are considered.

Toward surface orbitronics: giant orbital magnetism from the orbital Rashba effect at the surface of sp-metals

As the inversion symmetry is broken at a surface, spin-orbit interaction gives rise to spin-dependent energy shifts – a phenomenon which is known as the spin Rashba effect. Recently, it has been recognized that an orbital counterpart of the spin Rashba effect – the orbital Rashba effect – can be realized at surfaces even without spin-orbit coupling. Here, we propose a mechanism for the orbital Rashba effect based on sp orbital hybridization, which ultimately leads to the electric polarization of surface states. For the experimentally well-studied system of a BiAg2 monolayer, as a proof of principle, we show from first principles that this effect leads to chiral orbital textures in k-space. In predicting the magnitude of the orbital moment arising from the orbital Rashba effect, we demonstrate the crucial role played by the Berry phase theory for the magnitude and variation of the orbital textures. As a result, we predict a pronounced manifestation of various orbital effects at surfaces, and proclaim the orbital Rashba effect to be a key platform for surface orbitronics.

Giant tunable Rashba spin splitting in a two-dimensional BiSb monolayer and in BiSb/AlN heterostructures

Search of novel two-dimensional giant Rashba semiconductors is a crucial step in the development of the forthcoming nano-spintronics technology. Using first-principle calculations, we study a stable two-dimensional crystal phase of BiSb having buckled honeycomb lattice geometry, which is yet unexplored. The phonon, room temperature molecular dynamics and elastic constant calculations verify the dynamical and mechanical stability of the monolayer at 0~K and at room temperature. The calculated electronic bandstructure reveals the direct bandgap semiconducting nature of BiSb monolayer with presence of highly mobile two-dimensional electron gas (2DEG) near Fermi-level. Inclusion of spin-orbit coupling (SOC) yields the giant Rashba spin-splitting of 2DEG near Fermi-level. The calculated Rashba energy and Rashba splitting constant are 13 meV and 2.3 eV\AA, respectively. The strength of the Rashba splitting is amongst the largest yet known 2D Rashba semiconductors. We demonstrate that the strength of the Rashba spin-splitting can be significantly tuned by applying in-plane bi-axial strain on the BiSb monolayer. Presence of the giant Rashba spin-splitting together with the large electronic bandgap (1.6 eV) makes this system of peculiar interest for optoelectronics applications. Furthermore, we study the electronic properties of BiSb/AlN heterostructures having a lattice mismatch of 1.3\% at the interface. Our results suggest that BiSb monolayer and heterostructure systems could be potentially used to develop highly efficient spin field-effect transistors, optoelectronics and nano-spintronics devices. Thus, this comprehensive study of two-dimensional BiSb systems can expand the range of possible applications in the future spintronics technology.

Design, development and characterization of transdermal patch of methadone

The methadone has been the standard treatment for opioid addiction since the 1960s. In addition, methadone antagonizes the NMDA receptor and inhibits the reuptake of serotonin and norepinephrine. The methadone effects are in the central nervous system (CNS) and peripheral, its agonist μ action gives analgesic activity and its NMDA action and the inhibitions over monoamines can has a relevant paper in neuropathic pain treatment. Transdermal patch of methadone was prepared to improve adherence by the patient and it could be an alternative in the treatment of the chronic pain. Therefore, the aim of this research study was to design a bio-adhesive monolayer system to be applied like methadone deposit. For this purpose, we tested a copolymer that is plastoid® and PVA. The prepared formulations were evaluated for various parameters like film thickness, content uniformity, water vapour permeability (WVP), microphotographic study, calorimetric analysis, in vitro release study and in vitro permeation study. However, problems were detected relating to drug transfer through the skin. These were solved by incorporating enhancers into the patch formulation. The chosen enhancer was DMSO, since it increased Methadone permeation by up to 70% in comparison with patches with no enhancer.

Conditioned Medium of Wharton's Jelly Derived Stem Cells Can Enhance the Cartilage Specific Genes Expression by Chondrocytes in Monolayer and Mass Culture Systems.

Purpose: Mesenchymal stem cells (MSCs) have been introduced for cell therapy strategies in osteoarthritis (OA). Despite of their capacity for differentiation into chondrocyte, there are some evidences about their life-threatening problem after transplantation. So, some researchers shifted on the application of stem cells conditioned medium. The goal of this study is to evaluate whether Wharton's jelly derived stem cell conditioned medium (WJSCs-CM) can enhance the gene expression profile by chondrocytes in monolayer and mass culture systems. Methods: Conditioned medium was obtained from WJSCs at fourth passage. Isolated chondrocytes were plated at density of 1×106 for both monolayer and high density culture. Then cells in both groups were divided into control (received medium) and experiment group treated with WJ-CM for 3 and 6 days. Samples were prepared to evaluate gene expression profile of collagen II, aggrecan, cartilage oligomeric matrix protein (COMP) and sox-9 using real-time RT-PCR. Results: After 3 days, Chondrocytes treated with WJSCs-CM expressed significantly higher level of genes compared to the control group in both culture systems. After 6 days, the expression of genes in monolayer cultivated chondrocytes was decreased but that of the mass culture were up-regulated significantly. Conclusion: WJ-SCs-CM can increase the expression of cartilage-specific genes and can be introduced as a promoting factor for cartilage regeneration.

Two-dimensional metal-phosphorus monohydrides

In the rapidly expanding field of two-dimensional (2D) materials, special attention is given to systems that can be stabilized as free-standing monolayers. Here we use density-functional theory calculations to show how a well-established synthesis route can prepare stable 2D sheets of P-based hydrides. In particular, we show that strongly exothermic topotactic reactions of suitable AlB2-like precursors produce 2D materials with stoichiometries CuPH, AuPH, AgPH and PdPH. This novel family of monolayer systems provides multifunctional building blocks for devices as it includes metals, semimetals (with Dirac-like cones) and semiconductors with small or wide energy band gaps.

EXCITONIC ABSORPTION IN GAPPED GRAPHENE SYSTEMS

Excitonic absorption in monolayer and bilayer graphene systems with opened energy gap in the field of laser radiation is investigated. The obtained value of excitonic binding energy in monolayer is in good agreement with the exact analytical solution. It is shown that the account of all tight binding parameters in bilayer graphene leads to an increase of exciton binding energy.

Combined use of periodic reaction field and coarse-grained molecular dynamics simulations. I. phospholipid monolayer systems

A periodic reaction field based on a linear-combination-based isotropic periodic sum (LIPS) method was applied for coarse-grained molecular dynamics simulations of zwitterionic lipid systems. In phospholipid monolayer systems with various number of lipid molecules, the density profile, lipid orientation and surface tension were mainly calculated using the periodic reaction field and Ewald sum. The results from the periodic reaction field were almost equal to that from the Ewald sum. It is concluded that the periodic reaction field method has a great possibility to provide a high accuracy in determining coarse-grained zwitterionic lipid systems.

Theoretically Manipulating Quantum Dots on Two-Dimensional TiO2 Monolayer for Effective Visible Light Absorption.

Low solar energy harvesting and conversion efficiency has become a major problem in solar energy science and engineering owing to the difficulty in capturing solar energy across the wide solar spectrum, especially in the visible light range. Inspired by the extraordinary properties of materials arising from decreased dimensions, in this study, we explore a nanocontact system formed by a two-dimensional (2D) TiO2 monolayer and II-VI semiconductor (CdX)13 (X = S, Se, and Te) nanocages for engineering the visible light absorption. The nanocontact system, via either Ti-X or Cd-O bond coupling mechanism, forms an ideal type II band alignment, where the stronger donor-acceptor coupling in the Ti-X contact system more efficiently relaxes the coupled geometry and helps it to couple to more electrons, therefore leading to an enhancement of the absorption peaks in the visible frequency range. On changing the element X in (CdX)13 from S to Se then Te, a red shift of the visible light absorption peaks accompanied by stimulating optical response of the whole nanocontact system was observed. Nanocontacting semiconductors comprising low-dimensional (CdX)13 nanocage@TiO2 monolayer systems, which promote charge separation and optical absorption in the visible range that arise from the effects of adsorbent nature, decreasing size, and efficient interfacial coupling mechanism, are therefore promising photovoltaic and photocatalytic materials.

Differentiation of oligodendrocyte progenitor cells from dissociated monolayer and feeder-free cultured pluripotent stem cells.

Oligodendrocytes myelinate axons and form myelin sheaths in the central nervous system. The development of therapies for demyelinating diseases, including multiple sclerosis and leukodystrophies, is a challenge because the pathogenic mechanisms of disease remain poorly understood. Primate pluripotent stem cell-derived oligodendrocytes are expected to help elucidate the molecular pathogenesis of these diseases. Oligodendrocytes have been successfully differentiated from human pluripotent stem cells. However, it is challenging to prepare large amounts of oligodendrocytes over a short amount of time because of manipulation difficulties under conventional primate pluripotent stem cell culture methods. We developed a proprietary dissociated monolayer and feeder-free culture system to handle pluripotent stem cell cultures. Because the dissociated monolayer and feeder-free culture system improves the quality and growth of primate pluripotent stem cells, these cells could potentially be differentiated into any desired functional cells and consistently cultured in large-scale conditions. In the current study, oligodendrocyte progenitor cells and mature oligodendrocytes were generated within three months from monkey embryonic stem cells. The embryonic stem cell-derived oligodendrocytes exhibited in vitro myelinogenic potency with rat dorsal root ganglion neurons. Additionally, the transplanted oligodendrocyte progenitor cells differentiated into myelin basic protein-positive mature oligodendrocytes in the mouse corpus callosum. This preparative method was used for human induced pluripotent stem cells, which were also successfully differentiated into oligodendrocyte progenitor cells and mature oligodendrocytes that were capable of myelinating rat dorsal root ganglion neurons. Moreover, it was possible to freeze, thaw, and successfully re-culture the differentiating cells. These results showed that embryonic stem cells and human induced pluripotent stem cells maintained in a dissociated monolayer and feeder-free culture system have the potential to generate oligodendrocyte progenitor cells and mature oligodendrocytes in vitro and in vivo. This culture method could be applied to prepare large amounts of oligodendrocyte progenitor cells and mature oligodendrocytes in a relatively short amount of time.

Influence of misorientation on graphene Moiré patterns

In this work the influence of film-substrate misorientation on the strain-induced ordering of graphene films on various metallic surfaces is examined using a mesoscopic continuum model and first-principles atomistic calculations. The periodicity and free energy of the Moir\'e patterns that emerge are studied as a function of film-substrate adhesion strength for misfit strains far from and close to an incommensurate-commensurate phase transition. Interestingly the lowest energy states are found to be at small but finite misorientation even though these states have a higher domain wall density than the zero-misorientation states. First-principles density functional theory calculations are used to connect the results with experimental findings in graphene epitaxy. This combination of mesoscopic and atomistic approaches can be applied to the study of a wide range of strained 2D material systems including the III-nitride monolayer systems.

Half-metallicity in hole-doped nitrogenated honey graphene: A first-principles study

We have investigated the structural, electronic and magnetic properties of hole-doped nitrogenated honey graphene by first-principles calculations. Remarkably, there exists a stable half-metallic ferromagnetism phase with the average spin magnetic moment per carrier of near 1.0 μB in this monolayer system as the carrier density increases from 0 to 1.5×1014 cm−2. With further increase of carrier density, the half-metal state vanishes, while the magnetic state remains until the carrier density reaches 4.5×1014 cm−2. Our analysis reveals that the predicted itinerant magnetism arises from an exchange splitting of the electronic states at the top of the valence band, where the density of states shows a van Hove singularity. In addition, we have also studied the electron-doped nitrogenated honey graphene, and find the magnetic features are similar to those of the hole-doped system. As synthesis of monolayer nitrogenated honey graphene was reported, half-metallicity of nitrogenated honey graphene are feasible.

Alternative therapies for metastatic breast cancer: multimodal approach targeting tumor cell heterogeneity.

One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse signals from the local microenvironment may also contribute to the induction of tumor growth and metastasis. Collectively, these factors must be strategically studied and targeted in order to develop an effective treatment protocol. Targeted multimodal approaches need to be strategically studied in order to develop a treatment protocol that is successful in controlling tumor growth and preventing metastatic burden. Breast cancer, in particular, presents a unique problem because of the variety of subtypes of cancer that can arise and the multiple drug targets that could be exploited. For example, the tumor stage and subtypes often dictate the appropriate treatment regimen. Alternate multimodal therapies should consider the importance of time-dependent drug administration, as well as targeting the local and systemic tumor environment. Many reviews and papers have briefly touched on the clinical implications of this cellular heterogeneity; however, there has been very little discussion on the development of study models that reflect this diversity and on multimodal therapies that could target these subpopulations. Here, we summarize the current understanding of the origins of intratumoral heterogeneity in breast cancer subtypes, and its implications for tumor progression, metastatic potential, and treatment regimens. We also discuss the advantages and disadvantages of utilizing specific breast cancer models for research, including in vitro monolayer systems and three-dimensional mammospheres, as well as in vivo murine models that may have the capacity to encompass this heterogeneity. Lastly, we summarize some of the current advancements in the development of multitarget therapeutics that have shown promising results in clinical and preclinical studies when used alone or in combination with traditional regimens of surgery, chemotherapy, and/or radiation.

DFT comparison of structural and electronic properties of graphene and germanene: monolayer and bilayer systems

Two-dimensional honeycomb systems such as graphene and graphene-related materials have attracted enormous technological interest due to the wide range of applications from composites to conductive coatings. Based on density functional calculations we present a comparison of structural and electronic properties of monolayer (and bilayer) graphene and germanene, particularly, germanene have been synthesized on MoS2 with the Dirac cone properties. Our results show that germanene prefers a buckled structural conformation, which is slight more stable respect to its planar conformation. The well-known structure of graphene is compared with the buckled and planar structures of germanene at level of local density approximation. Graphene and germanene, in monolayer pristine conformations, exhibit massless Dirac fermions close to the K point. However, in germanene the top valence and bottom conduction bands are found at lower energies respect to graphene corresponding bands. The Fermi velocity in germanene is around 30% lower compared to graphene. Bilayer graphene show an anisotropic Dirac cone, while in bilayer germanene a small band gap at K point of ∼0.05 eV is detected. Our results are found to be in agreement with previous theoretical reports, and these pretend to give a compressible description from fundamental point of view.

Modification of spin electronic properties of Fen/GaSe monolayer adsorption system

Group-ⅢA metal-monochalcogenides have been extensively studied due to their unique optoelectronic and spin electronic properties. To realize the device applications, modifying their magnetic properties is desirable. Atomic doping and vacancy defects have been proven to produce itinerant ferromagnetism and half-metallicity in GaSe monolayer. Relatively, the magnetic modification by adsorbing foreign atoms is rarely reported. Traditional ferromagnetic material, Fe element, possessing high electronic polarizability and high Curie temperature, becomes the best option of adsorbate. In this work, Fen(n=1, 2) atoms adsorbed GaSe monolayer systems are constructed, and the spin electronic properties are systematically studied through the density function theory. Based on the geometric configuration of fully relaxed 33 GaSe supercell, three highly symmetrical sites, i.e., the hollow site, the top site of Se atom, and the top site of Ga atom are inspected to search for the stable absorption positions of Fen atoms. Computation results of adsorption energies indicate that the top site of Ga atom is preferred for single Fe atom, and the hollow site near the first Fe adatom is the most stable site serving as adsorbing the second Fe atom. Based on the most stable configuration, the spin electronic properties are studied. For the single Fe adsorbed system, the valence band maximum moves to point, resulting in a direct-band-gap. The strong orbit coupling effect between Fe adatom and its nearest Ga and Se atoms causes un-coincident majority and minority spin channels. Two impurity bands are located near the Fermi level and contribute only to the minority spin channel, producing a half-metallicity with a 100% spin polarization in the system. Bader charge analysis and spin-resolved partial density of states suggest that the spin polarization is mainly attributed to the transfer of Fe-3d electrons, and the hybridizations of Fe-3d, Se-4p, and Ga-4p states. Charge transfer from the Fe adatom to GaSe generates an n-type doping and an antiferromagnetic coupling between Fe and vicinal Ga and Se atoms. For the two-Fe-atoms adsorbed GaSe monolayer, the spin electronic states are found to be mainly located between the two Fe adatoms, leading to the reduction of the charge transfer from Fe to GaSe ML. As the original single spin channel turns into two spin channels (majority spin channel and minority spin channel) near the Fermi level, the ferromagnetic coupling between Fe atom and the vicinal Se atoms turn into antiferromagnetic coupling and the spin polarization falls to 0%. Therefore, the spin properties of GaSe monolayer can be controlled by modifying the number of adsorbed Fe atoms. These results reveal the formation and transform of the spin electronic properties of typical ferromagnetic/GaSe adsorption system, which offers some advice for designing and constructing the two-dimensional spin nanostructures.

Sustained Release for St. John?s Wort: A Rational Idea?

Purpose: Aim of this study was to evaluate St. John’s wort (SJW) extract for its suitability to be formulated in a sustained release dosage form using Ze 117 as example extract. Methods: Hypericin as marker for naphtodianthrones and quercetin as marker for contained flavonoids in Ze 117 were evaluated for solubility through shake flask method and for in vitro permeability through Caco-2 monolayers. Furthermore, different intestinal segments were screened for absorption capacity of markers using an in situ rat model. Results: Over a physiological pH range, naphthodianthrones exhibited pH-dependent solubility profiles with best solubility at pH 6.8. In contrast, solubility of flavonoids was pH-independent. In Caco-2 monolayer system, low permeation was evident for naphthodianthrone hypericin, while the flavonoid quercetin showed high permeation. Results of in situ rat model showed absorption of hypericin and quercetin mainly in jejunum. Conclusion: SJW extract covers components with different physicochemical properties. Predominant absorption in rat intestinal segments indicated presence of an absorption window in small intestine. Furthermore, there is high drug concentration per single dose in combination with a complex extract mixture. Thus, development of a sustained release formulation for SJW extract is challenging.

Measurements of surface concentration and charge number per adsorbed molecule for a thiolipid monolayer tethered to the Au(111) surface by a long hydrophilic chain

The charge number per adsorbed molecule and surface concentration of 2,3-di-O-phytanyl-sn-glycero-1-octaethyleneglycol-D,L-α-lipoic acid ester (DPOL) at a Au(111) electrode surface was investigated by chronocoulometry using two different film deposition methods. First, a known amount of the thiolipid was transferred from the air-water interface of a Langmuir trough onto the gold electrode surface via a Langmuir-Blodgett (LB) deposition. The charge density measurements for this monolayer system were used to determine the charge number per adsorbed DPOL molecule (electrosorption valency). The observed electrosorption valency values of the adsorbed DPOL film were much lower than the expected number of transferred electrons for a simple reductive desorption process. In the second deposition method, charge densities were measured for the electrode covered by a self-assembled DPOL monolayer. The electrosorption valency values determined from the LB DPOL film were used to calculate the packing density of the DPOL molecules within the self-assembled monolayer. The surface concentration of the molecules within the thiol monolayer with octaethylene glycol chains gave similar results to a related thiolipid with tetraethylene glycol chains (DPTL). This new finding indicates that both of these molecules (DPTL and DPOL) assume a brush conformation in densely packed self-assembled monolayers.

Rigidity of polymer micelles affects interactions with tumor cells

Controlling the interaction of drug delivery systems (DDS) with tissues is critical for the success of therapies. Specifically in cancer, due to the high density of the tumors, tissue penetration of DDS is critical and may be challenging. In previous work we have shown that Solidified Polymer Micelles (SPMs) rapidly internalize into cells and tissues. Using AFM analysis, in the present work we measured differences in rigidity of SPM compared with Wet Polymer Micelles (WPM). We further examined whether the semi-solid form of hydrated SPMs has an effect on the interaction with tumor cells both in mono-layer systems and in multi-layer clusters of cells as spheroids. For that we have performed detailed characterization of SPM compared to WPM, including examinations of particle size, stability, drug release kinetics and cell transcytosis, in melanoma A-375 cells. Cell uptake measurements were done using fluorescent signal analysis, FACS and microscopy imaging, showing enhanced abilities of SPMs to penetrate cells and tissues. A simple physical model is presented that well agrees with the experiments and provides insight about the role of particle rigidity in the engulfment mechanism. We conclude that particle rigidity enhances cellular uptake and tissue penetration and that SPMs have a promising potential as an effective and highly permeable DDS. Our findings can be important in future rational design of DDS for particle adjustment to specific tissues and pathologies.

Synthesis and characterization of a material derived from 4-mercaptobenzoic acid: A novel platform for oligonucleotide immobilization

This paper reports the electrochemical modification of pencil carbon graphite electrodes with a polymeric material derived from 4-mercaptobenzoic acid. Acidic solutions (pH 0 and 5.02) yielded an insulating polymeric film with anionic permselective properties. Scanning Electron Microscopy (SEM) analysis showed a complete coverage of the carbon graphite electrodes with a laminar-like polymeric structure. Different characterization studies indicate that the carboxyl group remained unchanged since the absorbance peak and oxidation potential did not change with the increase in pH at the pKa accounting for the carboxyl/carboxylate redox transition. The functionalized matrix was activated using carbodiimide, succinimide and an amine-modified oligonucleotide. The immobilization and hybridization processes were successfully verified using the redox electroactive indicator methylene blue, where better electrochemical signals were obtained when compared with the traditional self-assembled monolayer system. The selectivity of the system was verified using a noncomplementary target where no significant difference in electric current was observed when compared to the system containing only the probe. The method showed a good linear correlation coefficient (r2=0.9915), low limit of detection (1.17nmolL−1), and an acceptable precision (RSD=2.75%). The proposed method is suitable for further studies using different sequences of oligonucleotides.