Alessandra Scano

PEGylation and preliminary biocompatibility evaluation of magnetite–silica nanocomposites obtained by high energy ball milling.

High energy ball milling (HEBM) has been used for the first time to prepare PEGylated magnetite-silica (Fe(3)O(4)-SiO(2)) nanocomposites intended to be used for biological purposes. Surface amine groups were introduced by a silanization reaction involving 3-aminopropyl triethoxysilane (APTS) followed by PEGylation to yield long-term stable and stealth nanocomposites of 200nm in diameter. The efficient coverage by PEG chains was shown by isothermal titration calorimetry (ITC) where PEGylated nanocomposites did not interact with BSA compared to non-PEGylated counterparts which led to a significant change in enthalpy. By cell viability (MTT) assays and cell morphology investigations, it was evidenced that PEGylated Fe(3)O(4)-SiO(2) nanocomposites did not provide any appreciable cytotoxicity on J774 macrophage and MCF-7 breast cancer cell lines. Furthermore, noticeable internalization was evidenced by J774 cells with PEGylated Fe(3)O(4)-SiO(2) nanocomposites in contrast to MCF-7 cells, in good agreement with the respective tendency of each cell line for endocytosis.

Superparamagnetic blocking and superspin-glass freezing in ultra small δ-(Fe0.67Mn0.33)OOH particles

The magnetic properties of ultra-small (~2 nm) δ-(Fe(0.67)Mn(0.33))OOH nanoparticles prepared by a microemulsion technique have been investigated by magnetization and ac susceptibility measurements at variable frequency. The results provide evidence of two different magnetic regimes whose onset is identified by two maxima in the zero-field-cooled susceptibility: a large one, centered at ~150 K (T(mh)), and a narrow one at ~30 K (T(ml)). The two temperatures exhibit a different frequency dependence: T(mh) follows a Vogel-Fulcher law τ = τ(0)exp[(E(a)/k(B))/(T-T(0))], indicating a blocking of weakly interacting nanoparticle moments, whereas T(ml) follows a power law τ = τ(0)(T(g)/T(mν)-T(g))(α), suggesting a collective freezing of nanoparticle moments (superspin-glass state). This picture is coherent with the field dependence of T(ml) and T(mh) and with the temperature dependence of the coercivity, strongly increasing below 30 K.

Characterization of FeOOH nanoparticles and amorphous silica matrix in an FeOOH-Sio 2 nanocomposite

A nanocomposite with an FeOOH/SiO2 ratio equal to 17.7 wt% and the pertinent matrix, obtained by etching away the nanoparticles through reaction with hydrochloric acid, were investigated by XRD, TGA-DTA, heliostereopicnometry, BET, and TEM techniques. The study shows the presence in the nanocomposite of ferrihydrite nanoparticles phase with average dimensions around 4 nm. The FeOOH nanoparticles structure was analyzed by synchrotron X-ray diffraction data using the distribution difference curve method. The porous structure of the matrix resulting by etching away the nanoparticles differs significantly from that of a pure SiO2 sample obtained by hydrolysis of TEOS under the same operative conditions followed in the nanocomposite preparation.

Liposomes for (trans)dermal delivery of tretinoin: influence of drug concentration and vesicle composition

The influence of drug concentration and vesicle composition on the (trans)dermal delivery of tretinoin (TRA) was studied. To this purpose tretinoin was incorporated at different concentrations in unilamellar liposomes (UVs) prepared by sonication using phospholipids with different transition temperature (Tc): hydrogenated soy phosphatidylcholine (Tc = 51°C) or dipalmitoylphosphatidylcholine (Tc = 41°C). Vesicle dispersions were characterized in terms of morphology, size distribution and incorporation efficiency by using respectively optical and polarized light microscopy, transmission electron microscopy, dynamic laser light scattering, and HPLC. The effect of the vesicular incorporation of tretinoin at different molar ratios was investigated by zeta potential measurements and differential scanning calorimetry analysis. These analyses indicated that tretinoin principally interacts with the lipid groups until bilayer saturation. At higher concentration the ionized drug interacts with the polar head. Interactions between new-born pig skin and vesicle containing different amount of tretinoin were evaluated in vitro using Franz cells. The results obtained confirmed that liposomes saturated with TRA (molar fraction = 0.3) are capable of significantly promoting drug accumulation in the pig skin and that (trans)cutaneous delivery is strongly dependent on vesicular stability on the skin.

Diclofenac acid nanocrystals as an effective strategy to reduce in vivo skin inflammation by improving dermal drug bioavailability

In this work a diclofenac acid nanosuspension formulation was produced as a novel approach for the treatment of skin inflammation. Drug nanocrystals, prepared by the wet media milling technique and stabilized using Poloxamer 188, were characterized by different techniques: scanning electron microscopy, differential scanning calorimetry, X-ray powder diffractometry, Fourier transform infrared spectroscopy and photon correlation spectroscopy. The ability of nanocrystals to improve dermal drug bioavailability was investigated ex vivo by using Franz diffusion vertical cells and mouse skin, in comparison with both diclofenac acid coarse suspensions and a commercial formulation. The topical anti-inflammatory activity of the drug nanosuspension was assessed in vivo by testing its effect compared to common inflammatory endpoints: i.e. the inhibition of chemically induced oedema and leucocyte infiltration (reflected in myeloperoxidase activity). Following the milling procedure, diclofenac nanocrystals exhibited a mean diameter of approximately 279nm, a low polydispersity index (∼0.17) and maintained the same polymorphic form of the starting bulk powder. When the drug nanosuspension was applied on the mouse skin it produced a higher accumulation of diclofenac in the skin compared to both the coarse suspensions and the commercial formulation, as demonstrated by ex vivo transdermal delivery experiments. Moreover, the nanosuspension provided an in vivo oedema inhibition of 50%, which was not statistically different from the commercial formulation. On the contrary, the nanosuspension showed a higher inhibition of myeloperoxidase activity in the damaged tissue (86%) than the commercial formulation (16%).

Characterization and cytotoxicity studies on liposome–hydrophobic magnetite hybrid colloids

The aim of this study was to highlight the main features of magnetoliposomes prepared by TLE, using hydrophobic magnetite, and stabilized with oleic acid, instead of using the usual hydrophilic magnetite surrounded by sodium citrate. These biocompatible magnetoliposomes (MLs) were prepared with the purpose of producing a magnetic carrier capable of loading either hydrophilic or lipophilic drugs. The effect of different liposome/magnetite weight ratios on the stability of magnetoliposomes was evaluated by monitoring the mean diameter of the particles, their polydispersity index, and zeta potential over time. The prepared magnetoliposomes showed a high liposome-magnetite association, with magnetoliposomes containing PEG (polyethylene glycol) showing the best magnetite loading values. To verify the position of magnetite nanoparticles in the vesicular structures, the morphological characteristics of the structures were studied using transmission electron microscopy (TEM). TEM studies showed a strong affinity between hydrophobic magnetite nanoparticles, the surrounding oleic acid molecules, and phospholipids. Furthermore, the concentration above which one would expect to find a cytotoxic effect on cells as well as morphological cell-nanoparticle interactions was studied in situ by using the trypan blue dye exclusion assay, and the Prussian Blue modified staining method.

Drug silica nanocomposite: preparation, characterization and skin permeation studies

The aim of this work was to evaluate silica nanocomposites as topical drug delivery systems for the model drug, caffeine. Preparation, characterization, and skin permeation properties of caffeine-silica nanocomposites are described. Caffeine was loaded into the nanocomposites by grinding the drug with mesoporous silica in a ball mill up to 10 h and the efficiency of the process was studied by XRPD. Formulations were characterized by several methods that include FTIR, XRPD, SEM and TEM. The successful loading of caffeine was demonstrated by XRPD and FTIR. Morphology was studied by SEM that showed particle size reduction while TEM demonstrated formation of both core-shell and multilayered caffeine-silica structures. Solid-state NMR spectra excluded chemical interactions between caffeine and silica matrix, thus confirming that no solid state reactions occurred during the grinding process. Influence of drug inclusion in silica nanocomposite on the in vitro caffeine diffusion into and through the skin was investigated in comparison with a caffeine gel formulation (reference), using newborn pig skin and vertical Franz diffusion cells. Results from the in vitro skin permeation experiments showed that inclusion into the nanocomposite reduced and delayed caffeine permeation from the silica nanocomposite in comparison with the reference, independently from the amount of the tested formulation.

Formation of metallic silver and copper in non-aqueous media by ultrasonic radiation

Concentrated suspensions of silver and copper salts in silicone oil were heated to 200 °C and irradiated with ultrasonic energy for different time durations. Characterization of the products was done using X-ray powder diffraction. In most cases, metallic Ag or Cu were obtained, together with their oxide forms Ag2O and Cu2O. The salts, used as precursors, do not dissolve in silicone oil but rather form a heterogeneous system, and we assume that local heating, caused by the acoustic cavitation, enhanced their thermal decomposition and the formation of metallic particles. It was found that the presence of silver particles enhances the formation of metallic copper. This phenomenon was observed in the experiment with the acetate salts mixture.

Novel drug delivery systems for natural extracts: The case study of Vitis Vinifera extract-SiO2 nanocomposites

Graphical abstract Figure. No Caption available. ABSTRACT Ball Milling technique has been used to prepare for the first time Vitis Vinifera extract‐silica nanocomposites (VV‐SiO2 NCs), which combine the pharmacological effects of the extract with the effectiveness of silica as drug delivery system and active component in the treatment of wound healing. Different contents (1.0, 9.0 and 33.0 wt%) of Vitis Vinifera ethanolic extract were loaded into the silica matrix by grinding the extract with fumed silica using a planetary mill apparatus. The effect of the starting mixture composition and milling time on the final products was examined. The efficiency of the milling process was studied by X‐ray Powder Diffraction, Nuclear Magnetic Resonance, and Infrared Spectroscopy, indicating that the natural extract was not affected by the increasing of the milling time. The successful loading of the extract was demonstrated by Nitrogen adsorption/desorption measurements, which showed a decrease in the SSA and pore volume of the silica with the increasing of the extract amount. Morphology of the nanocomposites, investigated by Scanning Electron Microscopy, showed an increased agglomeration in the nanocomposites with the increment of the VV extract amount. Studies on the total phenol quantification and antioxidant activity of the natural extract before and after incorporation in the silica matrix were also carried out. The obtained results indicate that the milling process does not alter the VV extract components, which result to be embedded in the silica matrix. An increase of the antioxidant activity with the increment of the extract amount in the nanocomposites, up to values comparable to the pure VV extract, was also observed.

Mechanosynthesis of coordination polymers based on dithiophosphato and dithiophosphonato NiII complexes and 1,4-di(3-pyridinyl)buta-1,3-diyne ligand

Abstract In recent decades the mechanosynthesis of Coordination Polymers (CPs) has consolidated as a powerful method for the formation of coordination bonds. The aim of this study regards the environmental friendly mechanosynthesis of coordination polymers by milling the neutral square planar NiII complexes [((MeO)2PS2)2Ni] (1), [((EtO)2PS2)2Ni] (2), [((MeO–C6H4)(MeO))PS2)2Ni] (3), [((MeO–C6H4)(EtO))PS2)2Ni] (4), with the organic ligand 1,4-di(3-pyridyl)buta-1,3-diyne (L). Using these substrates, several mechanosynthesis were performed via Net Grinding (NG) and Liquid Assisted Grinding (LAG) approaches. A mechanochemical trend concerning the general inverse correlation between melting point of reagents and reactivity has been observed, highlighting a possible mechanism for these reactions under mechanical conditions.