Controlled and local drug delivery systems of anti‐inflammatory agents are attracting increasing attention thanks to their possible pharmaceutical and biomedical applications. These systems have ...extended therapeutic effects and reduced side effects.
The aim of this work is to synthesize a system composed of SiO2 glass and ketoprofen, an anti‐inflammatory drug, by the sol–gel process. Two different percentages (5 and 15 wt%) of drug are entrapped in the silica matrix via the sol–gel method and the dried material are analyzed via Fourier transform infrared spectroscopy (FTIR) and simultaneous Differential Scanning Calorimetery/Thermogravimetric analysis (DSC/TGA). The drug release kinetics of the amorphous bioactive materials are investigated. Molecular Mechanics and Molecular Dynamics simulations are currently in progress to investigate possible interactions between the silica‐based surface and the ketoprofen molecules both at low and high concentration for comparison with experimental data.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Using Molecular Mechanics and Molecular Dynamics methods, we investigated at the atomistic level the topography effects both on physisorption on different crystalline planes of TiO2 anatase and on ...the competitive adsorption when three different crystallographic faces were simultaneously present in an idealized nanosized crystal interacting with a simple heteroaromatic molecule experimentally used in sunlight-induced photosynthetic reaction.
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•Novel nanoassemblies of amphiphilic cyclodextrin and curcumin with high dispersibility in water were prepared.•Amphiphilic cyclodextrin/curcumin nanoassemblies were characterized by ...UV/Vis, Fluorescence and DLS.•Theoretical studies by MM and MD revealed at atomistic level the formation of amphiphilic cyclodextrin/curcumin nanoassembly.•In vitro studies on cancer cells pointed out the complexes suitability as promising nanoadjuvants in anticancer therapy.
Curcumin (Curc) and its derivatives have been extensively used as natural adjuvants in different pathologies including cancer, cardiovascular disease, Alzheimer’s disease, etc. Nowadays research is focused on formulations based on Curc to improve pharmacokinetics, bioavailability, overcoming its low water solubility and instability. Within our ongoing research on nanooncologicals based on amphiphilic cyclodextrins (aCD), here we propose nanoassemblies based on non-ionic aCD (SC6OH) entrapping Curc (SC6OH/Curc) as nanocomplex adjuvant in anticancer therapy. Nanoassemblies were prepared, at maxima entrapment efficiency, in aqueous dispersion at Curc/SC6OH 2:1 M ratio (up to Curc = 200 µM that is 0.073 mg/mL) by solvent evaporation method and characterized by complementary spectroscopic techniques, by studying stability and release kinetic. Theoretical studies based on Molecular Mechanics (MM) and Molecular Dynamics (MD) methods were performed to understand at atomistic level the formation of SC6OH/Curc nanoassemblies, the stability and the dispersibility of the Curc within the aggregates. Finally, SC6OH/Curc was tested in five different cancer cell lines (A2780, A549, MDA-MB-231, MDA-MB-453 and HepG2) showing similar IC50 values vs free Curc dissolved in DMSO. All these results open the routes to the development of new highly water dispersible nanodrugs based on cyclodextrin and curcuminoids for controlled drug delivery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tuning the self-assembly of dendritic amphiphiles represents a major challenge for the design of advanced nanomaterials for biomimetic applications. The morphology of the final aggregates, in fact, ...critically depends on the primary structure of the dendritic building blocks as well as the environmental conditions. Here we report a new family of fluorinated Janus-type dendrimers (FJDs), based on a short-chain and branched fluorinated synthon with 27 magnetically equivalent fluorine atoms, linked to bis-MPA polyester dendrons of different generations. Increasing size, flexibility, and number of peripheral hydroxyl groups, we observed a peculiar self-assembly behavior in bulk and in aqueous media as a consequence of the subtle balance between their fluorinated and hydrophilic portions. The lowest generation FJDs formed spherical nanoparticles in water, e.g., micelles, showing a single 19F NMR peak with good signal-to-noise ratio and over time stability, making them promising as 19F-MRI traceable probes. The highest generation FJD, instead, presented an interesting morphological transition from multilamellar dendrimersomes to tubules as a consequence of a subtle balance of intra- and intermolecular forces that compete at the interface. Interestingly, a reduction of the local mobility of CF3 groups passing from dendrimersomes to tubules switches off the 19F NMR signal. The transition mechanism has been rationalized by coarse-grain simulations as well as demonstrated by using cosolvents of different nature (e.g., fluorinated) that promote conformational changes, ultimately reflected in the self-assembly behavior. Short and branched fluorinated chains have here been demonstrated as new moieties for the design of FJDs with tunable self-assembly behavior for potential applications as biocompatible 19F MRI probes in the construction of theranostic platforms.
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IJS, KILJ, NUK, PNG, UL, UM
Tuning the self-assembly of dendritic amphiphiles represents a major challenge for the design of advanced nanomaterials for biomimetic applications. The morphology of the final aggregates, in fact, ...critically depends on the primary structure of the dendritic building blocks as well as the environmental conditions. Here we report a new family of fluorinated Janus-type dendrimers (FJDs), based on a short-chain and branched fluorinated synthon with 27 magnetically equivalent fluorine atoms, linked to bis-MPA polyester dendrons of different generations. Increasing size, flexibility, and number of peripheral hydroxyl groups, we observed a peculiar self-assembly behavior in bulk and in aqueous media as a consequence of the subtle balance between their fluorinated and hydrophilic portions. The lowest generation FJDs formed spherical nanoparticles in water, e.g., micelles, showing a single 19F NMR peak with good signal-to-noise ratio and over time stability, making them promising as 19F-MRI traceable probes. The highest generation FJD, instead, presented an interesting morphological transition from multilamellar dendrimersomes to tubules as a consequence of a subtle balance of intra- and intermolecular forces that compete at the interface. Interestingly, a reduction of the local mobility of CF3 groups passing from dendrimersomes to tubules switches off the 19F NMR signal. The transition mechanism has been rationalized by coarse-grain simulations as well as demonstrated by using cosolvents of different nature (e.g., fluorinated) that promote conformational changes, ultimately reflected in the self-assembly behavior. Short and branched fluorinated chains have here been demonstrated as new moieties for the design of FJDs with tunable self-assembly behavior for potential applications as biocompatible 19F MRI probes in the construction of theranostic platforms.
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IJS, KILJ, NUK, PNG, UL, UM
Using atomistic computer simulations, we study the adsorption of different globular protein fragments with different secondary structures on the surface of a hydrophilic glassy polymer, poly(vinyl ...alcohol), or PVA, and compare the results with our earlier calculations on hydrophobic graphite. The simulations were mainly carried out with implicit solvent in an effective dielectric medium by energy minimizations and molecular dynamics at room temperature. We find that on the hydrophilic PVA surface the fragments basically retain their globular shape with an incomplete denaturation, at variance with our earlier results for the same fragments on graphite. Correspondingly, the interaction energy between the fragments and the surface is significantly smaller than on graphite, both because less residues are in contact with the surface, and because they interact more weakly. Moreover, very few hydrogen bonds are formed between the adsorbate and the PVA surface, since both the protein fragments and the polymer chains separately optimize these interactions. Additional molecular dynamics simulations in explicit solvent were also performed to study the hydration of the adsorbed fragments and to estimate the possible solvation effects.
This paper reports a molecular modeling study of complex formation and aggregation behavior of a supramolecular system comprising three different moieties forming two distinct molecules. One molecule ...is a phenol derivative of porphyrin conjugated to a macrocyclic oligosaccharide, β-cyclodextrin (β-CD), and the other is 1-adamantanol (ADM). The inclusion complex of the latter molecule with the porphyrin–β-cyclodextrin (β-CD) conjugate, and the dimeric aggregates of the conjugate both in the presence and in the absence of the guest are investigated through molecular mechanics and molecular dynamics methods in vacuo, since the systems are scarcely soluble in polar solvents. In this way, we can find the most likely geometry of the complexes or aggregates and characterize the competitive inclusion behavior of ADM and of a porphyrin phenol within the β-CD cavity in terms of the various energy contributions stabilizing the resulting aggregates and/or inclusion complexes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Many important drugs in pharmaceutical applications are poorly soluble. Solubilization, which is diffusion through biological barriers, and the control of local administration are crucial steps for ...bioavailability and to avoid cytotoxic effects. Hybrid organic/inorganic biomaterials can incorporate drugs for in situ release after implantation. Molecular Mechanics (MM) and Molecular Dynamics (MD) simulations are useful tools for investigating intermolecular interactions between drug and biomaterial surfaces at the atomistic level for these applications. This work studies quercetin, a flavonoid drug important for its anti-inflammatory, antioxidant, and anticancer properties, and the amorphous SiO2 surface using a simulation protocol proposed in previous work related to ketoprofen drugs. After adsorption on the amorphous silica surface, the adsorption process of quercetin drug molecules at two different drug concentrations near a hydrated and then dried silica surface is investigated. Interestingly, these theoretical results are compared with experimental data obtained via Fourier Transform Infrared Spectroscopy (FT–IR) spectra related to quercetin molecules homogenously entrapped in a silica matrix obtained via the Sol–Gel method. Favorable H– bonds and some π–π interactions among drug molecules are crucial surface interactions for the new generation of biocompatible materials capable of incorporating anti-inflammatory agents for release into the human body.
The sequential adsorption of two proteins of the same or of an unlike nature on a heterogeneous hydrophobic surface is investigated through atomistic molecular dynamics simulations. By modeling two ...real protein fragments having a different secondary structure (alpha-helices or beta-sheets) on a graphite surface, the pre-adsorbed polypeptides are shown to modify the hydropathy of this substrate. Therefore, the graphite surface modified by the first adsorbed protein becomes more similar to a hydrophilic one in terms of both the interaction energy and the size of the second protein after the possible surface spreading.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UL, UM, UPUK, VKSCE, ZAGLJ
