scholarly journals Effect of the Incorporation of Functionalized Cyclodextrins in the Liposomal Bilayer

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1387 ◽  
Author(s):  
Romina Zappacosta ◽  
Benedetta Cornelio ◽  
Serena Pilato ◽  
Gabriella Siani ◽  
François Estour ◽  
...  
Keyword(s):  
Aqueous Solubility ◽  
Biologically Active ◽  
Cyclodextrin Complexes ◽  
Membrane Viscosity ◽  
Head Groups ◽  
Different Temperatures ◽  
Dynamics Simulations ◽  
Colloid Systems ◽  
Synthetic Derivatives ◽  
Liposome Stability

Liposomes loaded with drug–cyclodextrin complexes are widely used as drug delivery systems, especially for species with low aqueous solubility and stability. Investigation of the intimate interactions of macrocycles with liposomes are essential for formulation of efficient and stable drug-in-cyclodextrin-in-liposome carriers. In this work, we reported the preparation of unilamellar vesicles of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) embedded with native β-cyclodextrin and two synthetic derivatives: heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMCD) and heptakis(2,3-di-O-acetyl)-β-cyclodextrin (DACD). We then studied the effect of these macrocycles on the liposomal size, membrane viscosity, and liposomal stability at different temperatures and concentrations. We observed that TMCD and DACD affected vesicle size and the change of size was related to CD concentration. Irrespective of its nature, the macrocycle established interactions with the phospholipidic head groups, preventing cyclodextrins to diffuse into the lipid bilayer, as confirmed by molecular dynamics simulations. Such supramolecular structuring improves liposome stability making these colloid systems promising carriers for biologically active compounds.

Dislocation Generation and Crack Propagation in Metals Examined in Molecular Dynamics Simulations

1992 ◽  
Vol 278 ◽  
Author(s):  
J. A. Rifkin ◽  
C. S. Becquart ◽  
D. Kim ◽  
P. C. Clapp
Keyword(s):  
Crack Propagation ◽  
Atomistic Simulations ◽  
Many Body ◽  
Dislocation Generation ◽  
Embedded Atom ◽  
Stress Levels ◽  
Different Temperatures ◽  
The Many ◽  
Dynamics Simulations ◽  
Many Body Interactions

AbstractWe have carried out a series of atomistic simulations on arrays of about 10,000 atoms containing an atomically sharp crack and subjected to increasing stress levels. The ordered stoichiometric alloys B2 NiAl, B2 RuAl and A15 Nb3AI have been studied at different temperatures and stress levels, as well as the elements Al, Ni, Nb and Ru. The many body interactions used in the simulations were derived semi-empirically, using techniques related to the Embedded Atom Method. Trends in dislocation generation rates and crack propagation modes will be discussed and compared to experimental indications where possible, and some of the simulations will be demonstrated in the form of computer movies.

scholarly journals Improving the Solubilization and Bioavailability of Arbidol Hydrochloride by the Preparation of Binary and Ternary β-Cyclodextrin Complexes with Poloxamer 188

2021 ◽  
Vol 14 (5) ◽  
pp. 411
Author(s):  
Md. Khalid Anwer ◽  
Muzaffar Iqbal ◽  
Mohammad Muqtader Ahmed ◽  
Mohammed F. Aldawsari ◽  
Mohd Nazam Ansari ◽  
...  
Keyword(s):  
Antiviral Agent ◽  
Aqueous Solubility ◽  
Phase Solubility ◽  
Pharmacokinetic Studies ◽  
Solubility Curve ◽  
Cyclodextrin Complexes ◽  
Poloxamer 188 ◽  
The Stability

In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with β-cyclodextrin (β-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:β-CD and ADL/β-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:β-CD and ADL/β-CD with 1% poloxamer 188, respectively. The binary ADL/β-CD and ternary ADL/β-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/β-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and β-CD was confirmed by 1H NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/β-CD complexation in the presence of a third component, poloxamer 188.

scholarly journals The β-cyclodextrin/benzene complex and its hydrogen bonds – a theoretical study using molecular dynamics, quantum mechanics and COSMO-RS

2013 ◽  
Vol 9 ◽  
pp. 118-134 ◽  
Author(s):  
Jutta Erika Helga Köhler ◽  
Nicole Grczelschak-Mick
Keyword(s):  
Molecular Dynamics ◽  
Quantum Mechanics ◽  
Hydrogen Bonds ◽  
Md Simulations ◽  
Benzene Molecule ◽  
Glucose Unit ◽  
Hand Orientation ◽  
Different Temperatures ◽  
Dynamics Simulations ◽  
The Right

Four highly ordered hydrogen-bonded models of β-cyclodextrin (β-CD) and its inclusion complex with benzene were investigated by three different theoretical methods: classical quantum mechanics (QM) on AM1 and on the BP/TZVP-DISP3 level of approximation, and thirdly by classical molecular dynamics simulations (MD) at different temperatures (120 K and 273 to 300 K). The hydrogen bonds at the larger O2/O3 rim of empty β-CDs prefer the right-hand orientation, e.g., O3-H…O2-H in the same glucose unit and bifurcated towards …O4 and O3 of the next glucose unit on the right side. On AM1 level the complex energy was −2.75 kcal mol−1 when the benzene molecule was located parallel inside the β-CD cavity and −2.46 kcal mol−1 when it was positioned vertically. The AM1 HOMO/LUMO gap of the empty β-CD with about 12 eV is lowered to about 10 eV in the complex, in agreement with data from the literature. AM1 IR spectra displayed a splitting of the O–H frequencies of cyclodextrin upon complex formation. At the BP/TZVP-DISP3 level the parallel and vertical positions from the starting structures converged to a structure where benzene assumes a more oblique position (−20.16 kcal mol−1 and −20.22 kcal mol−1, resp.) as was reported in the literature. The character of the COSMO-RS σ-surface of β-CD was much more hydrophobic on its O6 rim than on its O2/O3 side when all hydrogen bonds were arranged in a concerted mode. This static QM picture of the β-CD/benzene complex at 0 K was extended by MD simulations. At 120 K benzene was mobile but always stayed inside the cavity of β-CD. The trajectories at 273, 280, 290 and 300 K certainly no longer displayed the highly ordered hydrogen bonds of β-CD and benzene occupied many different positions inside the cavity, before it left the β-CD finally at its O2/O3 side.

scholarly journals Membrane potential and dynamics in a ternary lipid mixture: insights from molecular dynamics simulations

2018 ◽  
Vol 20 (23) ◽  
pp. 15841-15851 ◽  
Author(s):  
Xubo Lin ◽  
Vinay Nair ◽  
Yong Zhou ◽  
Alemayehu A. Gorfe
Keyword(s):  
Molecular Dynamics ◽  
Membrane Potential ◽  
Molecular Dynamics Simulations ◽  
Transmembrane Potential ◽  
Lipid Mixture ◽  
Structure And Dynamics ◽  
Head Groups ◽  
Acyl Chains ◽  
Dynamics Simulations

Transmembrane potential modulates the structure and dynamics of lipid head-groups and acyl chains.

scholarly journals Progress to Improve Oral Bioavailability and Beneficial Effects of Resveratrol

2019 ◽  
Vol 20 (6) ◽  
pp. 1381 ◽  
Author(s):  
Adele Chimento ◽  
Francesca De Amicis ◽  
Rosa Sirianni ◽  
Maria Sinicropi ◽  
Francesco Puoci ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Aqueous Solubility ◽  
In Vivo Studies ◽  
Beneficial Effects ◽  
Lipid Nanocarriers ◽  
Methodological Approaches ◽  
Neuroprotective Actions ◽  
Synthetic Derivatives

Resveratrol (3,5,4′-trihydroxystilbene; RSV) is a natural nonflavonoid polyphenol present in many species of plants, particularly in grapes, blueberries, and peanuts. Several in vitro and in vivo studies have shown that in addition to antioxidant, anti-inflammatory, cardioprotective and neuroprotective actions, it exhibits antitumor properties. In mammalian models, RSV is extensively metabolized and rapidly eliminated and therefore it shows a poor bioavailability, in spite it of its lipophilic nature. During the past decade, in order to improve RSV low aqueous solubility, absorption, membrane transport, and its poor bioavailability, various methodological approaches and different synthetic derivatives have been developed. In this review, we will describe the strategies used to improve pharmacokinetic characteristics and then beneficial effects of RSV. These methodological approaches include RSV nanoencapsulation in lipid nanocarriers or liposomes, nanoemulsions, micelles, insertion into polymeric particles, solid dispersions, and nanocrystals. Moreover, the biological results obtained on several synthetic derivatives containing different substituents, such as methoxylic, hydroxylic groups, or halogens on the RSV aromatic rings, will be described. Results reported in the literature are encouraging but require additional in vivo studies, to support clinical applications.

scholarly journals The Droserasin 1 PSI: A Membrane-Interacting Antimicrobial Peptide from the Carnivorous Plant Drosera capensis

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1069
Author(s):  
Marc A. Sprague-Piercy ◽  
Jan C. Bierma ◽  
Marquise G. Crosby ◽  
Brooke P. Carpenter ◽  
Gemma R. Takahashi ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Disulfide Bonds ◽  
Lipid Vesicles ◽  
Carnivorous Plant ◽  
Nmr Studies ◽  
Biophysical Characterization ◽  
Head Groups ◽  
Wide Range ◽  
Dynamics Simulations ◽  
Lipid Nanodiscs

The Droserasins, aspartic proteases from the carnivorous plant Drosera capensis, contain a 100-residue plant-specific insert (PSI) that is post-translationally cleaved and independently acts as an antimicrobial peptide. PSIs are of interest not only for their inhibition of microbial growth, but also because they modify the size of lipid vesicles and strongly interact with biological membranes. PSIs may therefore be useful for modulating lipid systems in NMR studies of membrane proteins. Here we present the expression and biophysical characterization of the Droserasin 1 PSI (D1 PSI.) This peptide is monomeric in solution and maintains its primarily α -helical secondary structure over a wide range of temperatures and pH values, even under conditions where its three disulfide bonds are reduced. Vesicle fusion assays indicate that the D1 PSI strongly interacts with bacterial and fungal lipids at pH 5 and lower, consistent with the physiological pH of D. capensis mucilage. It binds lipids with a variety of head groups, highlighting its versatility as a potential stabilizer for lipid nanodiscs. Solid-state NMR spectra collected at a field strength of 36 T, using a unique series-connected hybrid magnet, indicate that the peptide is folded and strongly bound to the membrane. Molecular dynamics simulations indicate that the peptide is stable as either a monomer or a dimer in a lipid bilayer. Both the monomer and the dimer allow the passage of water through the membrane, albeit at different rates.

scholarly journals Sarin and Air Permeation Through a Nanoporous Graphene

MRS Advances ◽  
2020 ◽  
Vol 5 (27-28) ◽  
pp. 1475-1482
Author(s):  
Marco A. Maria ◽  
Alexandre F. Fonseca
Keyword(s):  
Room Temperature ◽  
Initial Pressure ◽  
Chemical Warfare Agent ◽  
The Other ◽  
Graphene Nanosheet ◽  
Different Temperatures ◽  
Nanoporous Graphene ◽  
Dynamics Simulations ◽  
And Storage ◽  
Air Permeation

ABSTRACTSarin gas is a dangerous chemical warfare agent (CWA). It is a nerve agent capable of bringing a person to death in about 15 minutes. A lethal concentration of sarin molecules in air is about 30 mg/m3. Experimental research on this gas requires very careful safety protocols for handling and storage. Therefore, theoretical and computational studies on sarin gas are very welcome and might provide important safe guides towards the management of this lethal substance. In this work, we investigated the interactions between sarin, air and nanoporous graphene, using tools of classical molecular dynamics simulations. Aiming to cast some light in the possible sarin selective filtration by graphene, we designed a bipartite simulation box with a porous graphene nanosheet placed at the middle. Sarin and air molecules were initially placed only on one side of the box so as to create an initial pressure towards the passage of both to the other side. The box dimensions were chosen so that the hole in the graphene was the only possible way through which sarin and air molecules can get to the other side of the box. The number of molecules that passed through the hole in graphene was monitored during 10 ns of simulation and the results for different temperatures were compared. The results show that, as far as the size of the holes are small, van der Waals forces between graphene and the molecules play a significant role on keeping sarin near graphene, at room temperature.

Deformation Behaviour of Single Linear Surface Defect Nickel Nanowire at Different Temperatures Studied by Molecular Dynamics Simulations

2020 ◽  
Vol 978 ◽  
pp. 428-435
Author(s):  
Krishna Chaitanya Katakam ◽  
Natraj Yedla
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Surface Defect ◽  
Deformation Behaviour ◽  
Stacking Faults ◽  
Effect Of Temperature ◽  
Dislocation Densities ◽  
Different Temperatures ◽  
Nickel Nanowire ◽  
Dynamics Simulations

The mechanical properties and deformation mechanism of nickel nanowire of dimension 100 Å (x-axis) × 1000 Å (y-axis) × 100 Å (z-axis) containing a single linear surface defect is studied at different temperatures using molecular dynamics simulations. The defect is created by deleting a row of atoms on the surface and is inclined at 25° to the loading axis. The tensile test is carried out at 0.01 K, 10 K, 100 K and 300 K temperature and 108 s-1strain rate. To determine the effect of temperature on the stress-strain curves, fracture and failure mechanism, a thorough investigation has taken place. Maximum strength of 21.26 GPa is observed for NW deformed at 0.01 K temperature and the strength decreased with increase in temperature. Through slip lines, the deformation relief pattern taken place by developing the extrusion areas along with intrusion over the surface defect area in all NWs deformed at respective temperatures. Further it is observed that fracture strains decrease with increase in temperature. After yielding, stacking faults associated with dislocations are generated by slip on all four {111} planes. Different type of dislocations with both intrinsic and extrinsic stacking faults are noticed. Out of all dislocation densities, Shockley partial dislocation densities has recorded a maximum value.

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