Surface Interactions between Ketoprofen and Silica‐Based Biomaterials as Drug Delivery System Synthesized Via Sol–Gel: A Molecular Dynamics Study

Biomaterial‐based drug delivery systems for a controlled drug release are drawing in‐ creasing attention thanks to their possible pharmaceutical and biomedical applications. It is im‐ portant to control the local administration of drugs, especially when the drug exhibits problems diffusing across biological barriers. Thus, in an appropriate concentration, it would be released in situ, reducing side effects due to interactions with the biological environment after implantation. A theoretical study based on Molecular Mechanics and Molecular Dynamics methods is performed to investigate possible surface interactions between the amorphous SiO2 surface and the ketoprofen molecules, an anti‐inflammatory drug, considering the role of drug concentration. These theoretical results are compared with experimental data obtained by analyzing, through Fourier transform infrared spectroscopy (FT‐IR), the interaction between the SiO2 amorphous surface and two per‐ centages of the ketoprofen drug entrapped in a silica matrix obtained via the sol–gel method and dried materials. The loaded drug in these amorphous bioactive material forms hydrogen bonds with the silica surface, as found in this theoretical study. The surface interactions are essential to have a new generation of biomaterials not only important for biocompatibility, with specific structural and functional properties, but also able to incorporate anti‐inflammatory agents for re‐ lease into the human bod

Aggregation behaviour of amphiphilic cyclodextrins: The nucleation stage by atomistic molecular dynamics simulations

Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a “bottom up” approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD), which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring molecules or by dispersion interactions at their lateral surface. We suggest that these aggregates can also form the nucleation stage of larger systems as well as the building blocks of micelles, vesicle, membranes, or generally nanoparticles thus opening new perspectives in the design of aggregates correlating their structures with the pharmaceutical properties

Molecular dynamics study of Sorafenib anti-cancer drug

Sorafenib (SOR) is an oral multikinase inhibitor which impedes proliferation, angiogenesis and invasion of cancer cells with low water-solubility. Amphiphilic cyclodextrins (aCD) have been investigated as a possible nanocarrier for systemic administration of SOR increasing its bio-availability [1]. A theoretical study about inclusion complexes of SOR drug and a model of aCD system using a simulation protocol based on Molecular Mechanics (MM) and Molecular Dynamics (MD) methods [2] is here reported. In this work we have studied at first the single model aCD (SC6OH, heptakis(2-O-oligo(ethylene oxide)-6-hexylthio)-β-CD bearing 14 units of ethylene-oxide at the CD secondary rim ) and the single molecule of SOR, then the formation of the complex in the dielectric environment [3]. The results data of final most stable geometry of the inclusion complex anticancer-cyclodextrin which showed the lowest potential and interaction energy were reported. The most stable host-guest geometry shows that the fluorine atoms of SOR drug are directed toward the hydrophobic primary rim of the aCD, while the part of the SOR rich in oxygen atoms is directed towards the hydrophilic secondary rim. References [1] M. L. Bondì, A. Scala, G. Sortino, E. Amore, C. Botto, A. Azzolina, D. Balasus, M. Cervello and A. Mazzaglia, Biomacromolecules, 2015, 16, 3784-3791. [2] G. Raffaini, F. Ganazzoli, L. Malpezzi, C. Fuganti, G. Fronza, W. Panzeri and A. Mele J. Phys. Chem B., 2009,113, 9110-9122

Modellazione molecolare di inibitori organici nel cemento (Molecular modeling of organic inhibitors in concrete)

Corrosion inhibitors are largely used to prevent chloride-induced corrosion in reinforced concrete structures. The interaction mechanisms with the passive film present on steel still requires deeper understanding. In a previous work [1] based on molecular mechanics and molecular dynamics methods [2-5] we considered organic inhibitors adsorbed on γ-FeOOH, comparing theoretical results with experimental data [1]. Here we considered the initial interaction with the inhibitor film and chlorides. In particular, the adsorbed tartrate monolayer show the best behavior thanks to the repulsions by the COO- groups exposed to chlorides, more distant from the γ-FeOOH surface, whereas the dimethylethanolamine film doesn’t have the same repulsion. The molecular simulations are a useful tool to better understand the behaviour of inhibitors in presence of chlorides that can start the corrosio

Aggregation behavior of amphiphilic cyclodextrins in a nonpolar solvent: Evidence of large-scale structures by atomistic molecular dynamics simulations and solution studies

Chemically modified cyclodextrins carrying both hydrophobic and hydrophilic substituents may form supramolecular aggregates or nanostructures of great interest. These systems have been usually investigated and characterized in water for their potential use as nanocarriers for drug delivery, but they can also aggregate in apolar solvents, as shown in the present paper through atomistic molecular dynamics simulations and dynamic light scattering measurements. The simulations, carried out with a large number of molecules in vacuo adopting an unbiased bottom-up approach, suggest the formation of bidimensional structures with characteristic length scales of the order of 10 nm, although some of these sizes are possibly affected by the assumed periodicity of the simulation cell, in particular at longer lengths. In any case, these nanostructures are stable at least from the kinetic viewpoint for relatively long times thanks to the large number of intermolecular interactions of dipolar and dispersive nature. The dynamic light scattering experiments indicate the presence of aggregates with a hydrodynamic radius of the order of 80 nm and a relatively modest polydispersity, even though smaller nanometer-sized aggregates cannot be fully ruled out. Taken together, these simulation and experimental results indicate that amphiphilic ally modified cyclodextrins do also form large-scale nanoaggregates even in apolar solvents

Polyetherimide(PEI)/SiO2 organic/inorganic composite: sol-gel synthesis, structural characterization, surface interactions

Polyetherimide (PEI), an amorphous thermoplastic material is a promising candidate for wide applications due to its high heat stability and its biocompatibility in human tissue. In the present paper, PEI (4 wt%) was added to SiO2 inorganic matrix in order to obtain a novel composite biomaterial through sol-gel route. Structural characterization of the biomaterial was provided by Fourier transform infrared spectroscopy (FTIR) that confirmed the presence of both organic and inorganic components in the structure. A theoretical study based on Molecular Mechanics and Molecular Dynamics methods will be useful in order to better understand the intermolecular interaction at the organic/inorganic interface compared with the discussed structural characterization. Concerning the compatibility in the biological system, a study of antibacterial properties was carried out. The effect of PEI/SiO2 composite on gram-negative bacterium Escherichia coli, was analyzed with a marked antimicrobial activity

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both 1/β-CD and 2/β-CD complexes, with the aromatic ring system entering the cavity from the large rim of the cyclodextrin and the alkylammonium chain protruding out of the cavity and facing the secondary OH rim. These features matched those found in the molecular dynamics (MD) simulations in solution and in the solid state from single-crystal X-ray diffraction of 1/β-CD and 2/β-CD complexes. The latter complex was found in a single conformation in the solid state, whilst the MD simulations in explicit water reproduced the conformational transitions observed experimentally for the free molecule

L-Arginine-Derived Polyamidoamine Oligomers Bearing at Both Ends beta-Cyclodextrin Units as pH-Sensitive Curcumin Carriers

The aza-Michael polyaddition of L-arginine and N,N′-methylene-bis-acrylamide gives the biocompatible and easily cell-internalized polyamidoamine ARGO7. By controlled synthesis, two ARGO7 oligomers, namely a trimer and a pentamer, bearing acrylamide terminal units, were obtained as precursors of the β-cyclodextrin-end-terminated oligomers P3 and P5, which have been shown to encapsulate curcumin at both pH 7.4 and 4.5. After lyophilization, P3- and P5-curcumin complexes gave stable water solutions. The apparent solubility of encapsulated curcumin was in the range 20–51 μg mL(−1), that is, three orders of magnitude higher than the water solubility of free curcumin (0.011 μg mL(−1)). The drug release profiles showed induction periods both at pH levels 4.5 and 7.4, suggesting a diffusive release mechanism, as confirmed by kinetic studies. The release rate of curcumin was higher at pH 7.4 than at pH 4.5 and, in both cases, it was higher for the P5 complex. Encapsulated curcumin was more photostable than the free drug. Molecular mechanics and molecular dynamics simulations explain at atomistic level the formation of aggregates due to favorable van der Waals interactions. The drug molecules interact with the external surface of carriers or form inclusion complexes with the β-cyclodextrin cavities. The aggregate stability is higher at pH 4.5