Simona Sapino

Role of particle coating in controlling skin damage photoinduced by titania nanoparticles

TiO2 nanoparticles hazard is associated to their photocatalytic activity causing release of DNA damaging ROS (Reactive Oxygen Species), lipid peroxidation and skin damage. Various coatings have been proposed to minimize photocatalysis, while keeping the potential to block UV radiations. Uncoated and variously coated commercial nano-titania have been classified on the basis of UVB-induced lipoperoxidation of linoleic acid. A selection of the most and the least protective specimens was then examined by ESR (Electron Spin Resonance) to evidence the presence of surface paramagnetic centres and the release of ROS in aqueous suspensions (spin trapping). Paramagnetic centres and ROS were correlated with the extent of lipid peroxidation. When tested on porcine skin (mimicking the human one), titania acted as on linoleic acid. The combined use of lipid peroxidation of simple fatty acids with ESR analysis is here proposed as a possible screening tool for the evaluation of the potential toxicity of nano-titania in sunscreen preparations.

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.

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.

Photostability and Stability over Time of Retinyl Palmitate in an O/W Emulsion and in SLN Introduced in the Emulsion

Solid lipid nanoparticles (SLNs) have been introduced as a novel carrier system for drugs and cosmetics. It has been found that SLNs themselves show physical UV‐blocking action. Cetyl palmitate, glyceryl behenate, and palmitic acid SLNs, all loaded with retinyl (vitamin A) palmitate, were prepared and introduced in an O/W emulsion. SLNs in O/W emulsion protect retinyl palmitate from the photo degradation induced by UVA and UVB radiation. This effect is probably due to the light‐scattering properties of SLN. Nanoparticles also protect vitamin A palmitate from thermal degradation. DSC thermal analytical examination, Z potential determination, and particle size measurement confirmed the solid character of the nanoparticles and the encapsulation of retinyl palmitate, their easy dispersion due to their negative charge on the surface, and their mean diameters in the nanometer range.

Photostability of Trolox in Water/Ethanol, Water, and Oramix CG 110 in the Absence and in the Presence of TiO2

Abstract Trolox (synthetic, hydrosoluble phenolic derivative of vitamin E, used as an active in cosmetic products) can undergo photooxidation upon UVB and UVA irradiation, the main degradation intermediate being Trolox C quinone. Trolox photodegradation rate decreases with decreasing polarity of the solvent, most likely because a more apolar environment inhibits oxidative processes. Ethanol is thus able to protect Trolox from degradation. Micellar solutions of Oramix CG 110® can incorporate Trolox in their core and protect it from photodegradation, either by providing an apolar environment or by competing for light absorption. Trolox can be degraded in the presence of titanium dioxide (an additive in many cosmetic products) under photocatalytic conditions, and both ethanol and Oramix show a certain protection effect towards Trolox photocatalytic degradation. However, concerning both direct photolysis and photocatalytic degradation, the protection given by ethanol and Oramix to Trolox results in at most 50% reduction of the transformation rate. Ethanol and Oramix (representative of the actual composition of cosmetic products) thus reduce but do not eliminate Trolox photodegradation. The solution to this problem might consist in the use of non‐transparent bottles for Trolox‐containing compounds and in the choice of titanium dioxide samples showing limited photocatalytic activity.

W/O/W Multiple Emulsions for Dermatological and Cosmetic Use, Obtained with Ethylene Oxide Free Emulsifiers

W/O/W multiple emulsions with ethylene oxide free emulsifiers, compatible with the skin, were prepared. They were fresh and easy to spread on the skin. The emulsion showed a shear thinning flux. Their multiplicity was confirmed with optical microscope analysis. FeSO4 and K3Fe(CN)6, when introduced separately in the inner and outer aqueous phases of the emulsions, did not give coloration, but when introduced together in the same aqueous phase, give a blue color due to their reaction. This experiment confirmed the multiplicity of these systems. The external aqueous phase of the emulsions was confirmed by Brilliant Blue up take from one of the multiple emulsions prepared higher than that from its W/O primary emulsion. The stability of the systems was confirmed by tests of breaking to centrifuge, of storage at 40°C and by freeze‐thaw cycles.

Specific effects of single antioxidants in the lipid peroxidation caused by nano-titania used in sunscreen lotions

The effect of some additives, phenylalanine, ascorbyl palmitate and sodium ascorbyl phosphate on the oxidation of linoleic acid and porcine ear skin induced by UV irradiation was investigated, in the absence and in the presence of variously uncoated and coated titania powders. Such additives have, on the one hand, a scavenging activity toward the oxidizing species photogenerated by TiO(2), and on the other one an inhibitory effect toward UVB-induced peroxidation. Sodium ascorbyl phosphate and ascorbyl palmitate displayed a stronger antioxidant effect than phenylalanine toward linoleic acid peroxidation. On porcine skin all the three molecules exhibited both antiradical and antioxidant activity. Their protective effect against peroxidation was higher with porcine skin lipids than with linoleic acid, referable to the chemical differences in the two lipid substrates.

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.