Ivana Miletto

Mesoporous silica as topical nanocarriers for quercetin: characterization and in vitro studies.

The flavonoid quercetin is extensively studied for its antioxidant and chemopreventive properties. However the poor water-solubility, low stability and short half-life could restrict its use in skin care products and therapy. The present study was aimed to evaluate the potential of aminopropyl functionalized mesoporous silica nanoparticles (NH2-MSN) as topical carrier system for quercetin delivery. Thermo gravimetric analysis, X-ray diffraction, high resolution transmission electron microscopy, nitrogen adsorption isotherms, FT-IR spectroscopy, zeta potential measurements and differential scanning calorimetry allowed analyzing with great detail the organic-inorganic molecular interaction. The protective effect of this vehicle on UV-induced degradation of the flavonoid was investigated revealing a certain positive influence of the inclusion on the photostability over time. Epidermal accumulation and transdermal permeation of this molecule were ex vivo evaluated using porcine skin mounted on Franz diffusion cells. The inclusion complexation with the inorganic nanoparticles increased the penetration of quercetin into the skin after 24h post-application without transdermal delivery. The effect of quercetin alone or given as complex with NH2-MSN on proliferation of JR8 human melanoma cells was evaluated by sulforhodamine B colorimetric proliferation assay. At a concentration 60 μM the complex with NH2-MSN was more effective than quercetin alone, causing about 50% inhibition of cell proliferation.

Stabilization of quercetin flavonoid in MCM-41 mesoporous silica: positive effect of surface functionalization

Antioxidants can prevent UV-induced skin damage mainly by neutralizing free radicals. For this purpose, quercetin (Q) is one of the most employed flavonoids even if the potential usefulness is limited by its unfavorable physicochemical properties. In this context, mesoporous silica (MCM-41) is herein proposed as a novel vehicle able to improve the stability and performance of this phenolic substrate in topical products. Complexes of Q with plain or octyl-functionalized MCM-41 were successfully prepared with different weight ratios by a kneading method, and then, they were characterized by XRD, gas-volumetric (BET), TGA, DSC, and FTIR analyses. The performances of the different complexes were evaluated in vitro in terms of membrane diffusion profiles, storage and photostability, antiradical and chelating activities. The physicochemical characterization confirmed an important host/guest interaction due to the formation of Si-OH/quercetin hydrogen-bonded adducts further strengthened by octyl functionalization through van der Waals forces. The immobilization of Q, particularly on octyl-functionalized silica, increased the stability without undermining the antioxidant efficacy opening the way for an innovative employment of mesoporous composite materials in the skincare field.

NIR Persistent Luminescence of Lanthanide Ion-Doped Rare-Earth Oxycarbonates: The Effect of Dopants

A series of luminescent rare-earth ion-doped hexagonal II-type Gd oxycarbonate phosphors Gd2-xRExO2CO3 (RE = Eu(3+), Yb(3+), Dy(3+)) have been successfully synthesized by thermal decomposition of the corresponding mixed oxalates. The Yb(3+) doped Gd-oxycarbonate has evidenced a high persistent luminescence in the NIR region, that is independent from the temperature and makes this materials particular attractive as optical probes for bioimaging.

Mesoporous silica as a carrier for topical application: the Trolox case study

As part of a recent research effort aimed at employing mesoporous materials for controlled drug delivery, this paper presents MCM-41 as a carrier for topical application, using Trolox as a model unstable guest molecule. The complexes between Trolox and MCM-41 were prepared by employing different inclusion procedures, varying solvent, method and pretreatment of the silica matrix. The objectives of this study were to determine Trolox loading, analyze its integrity and availability after immobilization on mesoporous silica, evaluate MCM-41 influence on Trolox photodegradation and establish whether the preparation method significantly influences complex properties. The characterization analyses (XRD, TGA, DSC and FTIR) confirmed the hydrogen-bonding interaction and Trolox structure preservation. Gas-volumetric analysis showed a consistent decrease in surface area and in pore volume and diameter with respect to bare MCM-41 indicating that Trolox was mainly located within mesopores. In vitro diffusion tests showed a slower release of Trolox after inclusion in the MCM-41 matrix; at the same time UV irradiation studies highlighted an increased photostability for the complex particularly in O/W emulsion. Moreover the radical scavenging activity of Trolox was maintained after immobilization. In all cases, differences were observed in all tested samples, suggesting that results could be optimized by modifying the inclusion procedure and by improving the guest loading.

MCM-41 as a useful vector for rutin topical formulations: Synthesis, characterization and testing

Rutin, the glycoside of quercetin, could be used in topical preparations because of its antioxidant and radical scavenging properties, but its employ in cosmetic and pharmaceutical products is limited by poor physico-chemical stability. These issues were addressed by preparing, characterizing and testing rutin inclusion complexes with MCM-41 mesoporous silica. The effect of surface functionalization with aminopropyl groups (NH₂-MCM-41) on the molecules properties was studied. The organic/inorganic interaction was confirmed by many techniques. In particular, the high inclusion of rutin in the pores of NH₂-MCM-41 was assessed by XRD, TGA, gas-volumetric analysis (BET), while FTIR spectroscopy allowed to analyse with great detail the molecular interaction with the inorganic surface. Rutin was stabilized against UV degradation, mostly by its inclusion in NH₂-MCM-41. Ex vivo studies showed a greater accumulation in porcine skin in the case of rutin complexed with NH₂-MCM-41. Not only antioxidant properties of rutin were maintained after immobilization but, with aminopropyl silica, the metal-chelating activity increased noticeably. The immobilization of rutin in aminopropyl silica resulted in better performance in terms of activity and photostability, suggesting the importance of functionalization in stabilizing organic molecules within silica pores.

Thermoresponsive mesoporous silica nanoparticles as a carrier for skin delivery of quercetin.

Recently, mesoporous silica nanoparticles (MSNs) have emerged as promising drug delivery systems able to preserve the integrity of the carried substance and/or to selectively reach a target site; however, they have rarely been explored for skin application. In this study, thermoresponsive MSNs, designed to work at physiologic cutaneous temperature, are proposed as innovative topical carriers for quercetin (Q), a well-known antioxidant. The thermosensitive nanoparticles were prepared by functionalizing two different types of matrices, with pore size of 3.5nm (MSNsmall) and 5.0nm (MSNbig), carrying out a free radical copolymerization of N-isopropylacrylamide (NIPAM) and 3-(methacryloxypropyl)trimethoxysilane (MPS) inside the mesopores. The obtained copolymer-grafted MSNs (copoly-MSNs) were physico-chemically characterized and their biocompatibility was attested on a human keratinocyte cell line (HaCaT). The release profiles were assessed and the functional activity of Q, free or loaded, was evaluated in terms of antiradical and metal chelating activities. Ex vivo accumulation and permeation through porcine skin were also investigated. The characterization confirmed the copolymer functionalization of the MSNs. In addition, both the bare and functionalized silica matrices were found to be biocompatible. Among the copolymer-grafted complexes, Q/copoly-MSNbig exhibited more evident thermoresponsive behavior proving the potential of these thermosensitive systems for advanced dermal delivery.

Functionalization of mesoporous MCM-41 with aminopropyl groups by co-condensation and grafting: a physico-chemical characterization

This work reports on the synthesis and characterization of NH2-MCM-41, a well-known hybrid material commonly used in biomedical and biotechnological applications, based on mesoporous silica and aminopropyl functionalities. Samples were prepared by post-synthesis grafting and by one-pot co-condensation methods, to achieve a relatively high organic loading (around 12% wt), and were characterized in terms of porosity, thermal stability and distribution of the aminopropyl moieties in the silica framework. The results suggest that grafting brings about an almost complete consumption of surface silanols, with structurally defined functional groups mainly located inside the material pores. In contrast, co-condensation results in lower surface area and thermal stability, with ink-bottle-like pores. This suggests that the aminopropyl groups are not only linked to the pores inner surface but could be located in the pore walls or at their entrance.

Delivery of Gemcitabine Prodrugs Employing Mesoporous Silica Nanoparticles

In this paper, mesoporous silica nanoparticles (MSNs) were studied as vehicles for the delivery of the antitumoral drug gemcitabine (GEM) and of its 4-(N)-acyl derivatives, (4-(N)-valeroyl-(C5GEM), 4-(N)-lauroyl-(C12GEM) and 4-(N)-stearoyl-gemcitabine (C18GEM)). The loading of the GEM lipophilic prodrugs on MSNs was explored with the aim to obtain both a physical and a chemical protection of GEM from rapid plasmatic metabolization. For this purpose, MSNs as such or with grafted aminopropyl and carboxyethyl groups were prepared and characterized. Then, their different drug loading capacity in relation to the nature of the functional group was evaluated. In our experimental conditions, GEM was not loaded in any MSNs, while C12GEM was the most efficiently encapsulated and employed for further evaluation. The results showed that loading capacity increased with the presence of functional groups on the nanoparticles; similarly, the presence of functional groups on MSNs’ surface influenced the drug release profile. Finally, the cytotoxicity of the different preparations was evaluated and data showed that C12GEM loaded MSNs are less cytotoxic than the free drug with an activity that increased with the incubating time, indicating that all these systems are able to release the drug in a controlled manner. Altogether, the results demonstrate that these MSNs could be an interesting system for the delivery of anticancer drugs.

Experimental and first-principles IR characterization of quercetin adsorbed on a silica surface

A combined experimental–theoretical study of quercetin adsorbed on a silica surface has been carried out in order to investigate the specific nature of their interaction. By means of an accurate hybrid functional PBE-D* approach, inclusive of dispersion interactions through the empirical D* Grimme’s term, the energetics of various configurations has been evaluated. IR spectra of the most probable ones, determined on the basis of thermodynamics considerations, have been simulated and compared to ad hoc measured spectra. A detailed classification of the peaks is proposed which sheds light onto some cloudy parts of the experimental IR spectra assignments. The most notable feature of our results is the extended and enhanced hydrogen-bonds network which is formed throughout the surface-molecule aggregate, thanks to the molecule acting as a bridge among the hydrogen bonds already present on the pristine silica surface.

Mesoporous Silica Scaffolds as Precursor to Drive the Formation of Hierarchical SAPO-34 with Tunable Acid Properties

Using a distinctive bottom-up approach, a hierarchical silicoaluminophosphate, SAPO-34, has been synthesized using cetyl trimethylammonium bromide (CTAB) encapsulated within ordered mesoporous silica (MCM-41) that serves as both the silicon source and mesoporogen. The structural and textural properties of the hierarchical SAPO-34 were contrasted against its microporous analogue, and the nature, strength, and accessibility of the Brønsted acid sites were studied using a range of physicochemical characterization tools; notably probe-based FTIR and solid-state magic angle spinning (SS MAS) NMR spectroscopies. Whilst CO was used to study the acid properties of hierarchical SAPO-34, bulkier molecular probes (including pyridine, 2,4,6-trimethylpyridine and 2,6-di-tert-butylpyridine) allowed particular insight into the enhanced accessibility of the acid sites. The activity of the hierarchical SAPO-34 catalyst was evaluated in the industrially-relevant, acid-catalyzed Beckmann rearrangement of cyclohexanone oxime to ϵ-caprolactam, under vapor-phase conditions. These catalytic investigations revealed a significant enhancement in the yield of ϵ-caprolactam using our hierarchical SAPO-34 catalyst compared to SAPO-34, MCM-41, or a mechanical mixture of these two phases. The results highlight the merits of our design strategy for facilitating enhanced mass transfer, whilst retaining favorable acid site characteristics.