Flaviano Testa

Drug delivery devices based on mesoporous silicate.

A mesoporous material based on aluminosilicate mixture was studied to investigate its ability to include drugs and then release them. Nonsteroidal anti-inflammatory agents such as diflunisal, naproxen, ibuprofen and its sodium salt have been used in this study. The preparation of the mesoporous material and its characterization by X-ray, N2 absorption-desorption isotherm, and thermogravimetry analysis have been described. Drug loading was performed by a soaking procedure. Drug-loaded matrices were characterized for entrapped drug amount, water absorption ability, and thermogravimetric behavior. Drug release studies also were performed at pH 1.1 and 6.8 mimicking gastrointestinal fluids. Experimental results showed that this type of matrix is able to trap the bioactive agents by a soaking procedure and, then, to release them in conditions mimicking the biological fluids. Also, the high affinity of these matrices for water makes them potentially biocompatible. Release data suggest that the matrix impregnated with diflunisal offers good potential as a system for the modified drug release.

PEG-templated mesoporous silica nanoparticles exclusively target cancer cells

Mesoporous silica nanoparticles (MSNs) have been proposed as DNA and drug delivery carriers, as well as efficient tools for fluorescent cell tracking. The major limitation is that MSNs enter cells regardless of a target-specific functionalization. Here we show that non functionalized MSNs, synthesized using a PEG surfactant-based interfacial synthesis procedure, do not enter cells, while a highly specific, receptor mediated, cellular internalization of folic acid (FOL) grafted MSNs (MSN-FOL), occurs exclusively in folate receptor (FR) expressing cells. Neither the classical clathrin pathway nor macropinocytosis is involved in the MSN endocytic process, while fluorescent MSNs (MSN-FITC) enter cells through aspecific, caveolae-mediated, endocytosis. Moreover, internalized particles seem to be mostly exocytosed from cells within 96 h. Finally, cisplatin (Cp) loaded MSN-FOL were tested on cancerous FR-positive (HeLa) or normal FR-negative (HEK293) cells. A strong growth arrest was observed only in HeLa cells treated with MSN-FOL-Cp. The results presented here show that our mesoporous nanoparticles do not enter cells unless opportunely functionalized, suggesting that they could represent a promising vehicle for drug targeting applications.

Silica-Based Mesoporous Materials as Drug Delivery System for Methotrexate Release

Antineoplastic methotrexate has been loaded through different soaking procedures on silica-based mesoporous materials and, successively, released mimicking an oral administration. The materials were prepared using a self-assembly mechanism in the presence of cationic surfactants with alkyl chain of 16, 12, and 10 carbon atoms in the synthesis mixture to obtain different pore diameter in the porous structure. Mesoporous materials were prepared as pure silica sample and in the presence of Al(OH)3 in the synthesis mixture. Only alumina-silica samples were able to load methotrexate. The amounts of drug loaded and the in vitro release kinetics are a function of the pore size of the materials.

Influence of cations on the physicochemical and structural properties of aluminosilicate gel precursors. Part 1. Chemical and thermal properties

The influence of the type of alkali cations on the properties of aluminosilicate gels were studied by chemical and thermal analyses of the solid phases precipitated from the batches of the following molar composition: 4.41 Me 2 O:Al 2 O 3 :3 SiO 2 :222.2 H 2 O, where Me + = Na + , Na + + K + , Na + + Li + , and K + . The change in the chemical composition of dry precipitates, influenced by the presence of different cations and their mixtures, is discussed with respect to the interaction of cations with silicate species in the solution and colloid chemistry of gelation processes. Analysis of kinetics of dehydration of gels as well as hydrothermal treatment of the gels confirmed the role of the sodium ion as a “structure-forming” cation and revealed that sodium ions cause the formation of structural subunits inside the gel matrix.

Synthesis of zeolite beta in presence of fluorides: Influence of alkali cations

The influence of alkali cations on the synthesis of zeolite Beta is systematically investigated in fluorine-containing media using the seeding method. Both initial gels and final crystalline samples were thoroughly characterized using XRD, chemical analysis, thermal analysis, and multi- n.m.r. ( 29 Si, 27 Al, and 13 C). The best crystalline samples were obtained after 15 days of crystallization at 170°C from gels of the following composition: 12.5 DABCO : 12.5 MA : x HF : y MF : z Al 2 O 3 : 25 SiO 2 : 500 H 2 O with x + y = 25 and M =NH 4 , Li, Na, K, and Cs. At high cation content ( y = 12.5), only NH 4 , Li, and Cs led to zeolite Beta. In the presence of Na and K fluorides, the amount of MF has to be decreased to synthesize pure zeolite Beta. From the analysis of both the induction and crystallization rates it was concluded that one of the main roles of the alkali cations is their electrostatic stabilization of the gel.

Attempts to produce uniform Fe(III) siting in various Fe-content ZSM-5 zeolites: Determination of framework/extra-framework ratio of Fe(III) in zeolites by EPR and Mössbauer spectroscopy

Abstract Fe(III)-content ZSM-5 catalysts play important role in selective redox reactions, like biomimetic oxidations, or selective catalytic reactions (SCR) of pollutants, dangerous for the environment. There is a dispute in the literature whether the catalytic activity of these materials is due to isomorphously substituting framework (FW) iron, or extra-framework (EFW) oxide/hydroxide material of high dispersity, not incorporated into the lattice during the synthesis, or became ejected from the framework following the post-synthesis treatments (calcination, heat-treatment). In either case it is a must to know the FW/EFW ratio in order to correlate the catalytic activity with the number of active sites, or active surface area of the catalyst ingredient. In the case of EFW iron only (introduced, e.g. by ion-exchange) the chemical identity, particle size, location and thereby the probability of attainment from the fluid phase(s) are uncertain. Isomorphic substitution is more complicated, because in addition to these even the FW/EFW ratio is questionable. From both practical and academic interest it would be advantageous (e.g. from the point of view of above correlation) to have uniform FW, or EFW Fe(III) siting, or when it is mixed, to know the FW/EFW ratio. The authors approach this problem from several directions: they elaborate various synthesis methods to minimise EFW iron; extract unwanted EFW iron by reducing/complexing agents (SO 2 , hydroxylamine), or, if necessary, reintroduce EFW iron by (liquid and solid) ion-exchange and monitor the changes thus produced in the FW and EFW iron contents by X-band EPR and Mossbauer spectroscopy. Using mathematical methods and sophisticated analysis of the sub-spectra (intensity dependence on the iron content and temperature), the EPR spectrum-deconvolution made possible to reinterpret the X-band EPR Fe(III) spectra in weak ligand-field media, like zeolites. If the total iron contents of samples are known (e.g. from XRF spectra) the FW/EFW ratio can be computed on the basis of the deconvoluted EPR spectra alone. These values are in very good agreement with similar estimates obtained from the Mossbauer spectra, proving that the Mossbauer “loudness” for the various iron components is nearly equal.

The influence of alkali cations on the synthesis of ZSM-5 in fluoride medium

Abstract The role of NH + 4 , Na + , K + and Cs + cations was investigated in the synthesis of ZSM-5 using fluoride as mineralizing agent. The amounts of aluminum and alkali cations were varied in gels of initial composition 10SiO 2 – x MF– y Al(OH) 3 –1.25TPABr–330H 2 O with M=NH 4 , Na, K and Cs, x =9, 15 and 24, y =0.16, 0.5 and 1.0 and TPABr=tetrapropylammonium bromide. The potassium-containing system is the most effective one with respect to incorporation of aluminum into the zeolite framework, while the ammonium-containing system is the least effective one. Crystallization patterns and crystal morphologies are strongly influenced by the nature of the fluoride salt added to the reaction mixture. The kinetic data show that the cations not only influence the reaction rates by their electrostatic interaction, but also due to their specific interaction with the fluoride anion in various siliceous and aluminosiliceous complexes.

Synthesis and characterization of Fe- and (Fe,Al )-MCM-22 zeolites

Abstract The synthesis of Fe-MCM-22 zeolite is reported for the first time. Its structure and characteristics are similar to those of the MCM-22 zeolite. The aluminum is in a framework tetrahedral position in the [Fe,Al]-MCM-22 samples. The white color of the samples, the increase of the 29 Si and 27 Al NMR linewidths with increasing Fe content and the constancy of the (Fe+Al)/u.c. values all suggest that Fe is also incorporated in tetrahedral position of the framework.

Self-incorporation of a luminescent neutral iridium(III) complex in different mesoporous micelle-templated silicas

The neutral luminescent tris-cyclometallated 2-phenylpyridine iridium(III) complex, (fac-Ir(ppy)3, [Ir]) following a self-assembling procedure, has been successfully located in the cavities of mesostructured silica materials through a surfactant-mediated process. Two different structure-directing agents, the cationic cetyltrimethyl ammonium bromide (CTAB) and the non-ionic poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P123) were tested. The structural features induced by the metal complex incorporation can be explained by comparing the newly synthesized hybrid mesostructured materials with the corresponding undoped samples which were similarly prepared. X-Ray powder diffraction (XRD), nitrogen sorption, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and UV-Vis spectroscopy were used to characterize the investigated materials. Medium-sized spherical particles of 800 nm were obtained using CTAB as a structure-directing agent whereas larger monolithic aggregates with a minimum dimension of 5–8 μm were obtained using P123. The new hybrids showed the typical hexagonal symmetry of analogously prepared materials. Moreover high luminescence quantum yield values were obtained for both hybrids as a result of a very good dispersion of the chromophore in the mesostructured matrices, thereby avoiding dramatic self-quenching phenomena. The approach described in this paper provides a simple synthetic way to prepare new luminescent silica-based materials by the inclusion of neutral metal-containing luminophores into the pores of a mesoporous hosting skeleton.

Synthesis and characterization of aluminosilicate MCM-22 in basic media in the presence of fluoride salts

MCM-22 zeolite was prepared using NaF and KF as mineralizing agents with an Si/Al ratio ranging from 15 to 30. The initial batch composition was aMF–bAl(OH)3–30SiO2–15HMI–1350H2O with M=NH4, Na, K or Cs; HMI=hexamethyleneimine ; 20≤a≤40 and 0.5≤b≤4. The increase of Si/Al in the initial mixture determines the crystallization of ZSM-51 and ZSM-35 zeolite type structures. However, the presence of NH4F and CsF did not promote the crystallization of any type of zeolite structure. MCM-22 zeolite was characterized by X-ray diffraction, proton-induced γ-ray emission, thermal analysis and multi-nuclear NMR techniques. Most samples were obtained in a pure form, where the aluminum atoms are incorporated in the tetrahedral sites of the MCM-22 structure. Several tetrahedral aluminum species could be identified by 27Al NMR. The 29Si NMR spectra showed some seven different lines. The 13C NMR spectra were characteristic of two different HMI molecules incorporated intact in the porous volume. Apart from the reaction rates and the crystal morphology, the characteristics of the MCM-22 samples are similar to those obtained in alkaline media only.