Elena Ugazio

Incorporation of cyclosporin A in solid lipid nanoparticles (SLN)

The cyclic undecapeptide cyclosporin A (CyA) a potent immunosuppressive drug used in many therapies, is extremely hydrophobic. Commercial products employ solubilising agents to improve gastrointestinal absorption. In the present study CyA solid lipid nanoparticles (SLN) are prepared from warm o/w microemulsion, dispersed in cold water. The matrix chiefly consists of stearic acid, phosphatidylcholine and taurocholate; up to 13% of CyA can be incorporated. The average diameter of CyA-loaded SLNs is below 300 nm and transmission electron microscopy (TEM) analysis shows them to be spherical. In vitro release of CyA from SLNs is low. CyA-loaded SLNs can be proposed for most administration routes, in particular for the duodenal route.

Thymopentin in solid lipid nanoparticles

Abstract The pentapeptide thymopentin was englobed in solid lipid nanoparticles prepared from warm microemulsions following two different methods: from O/W microemulsion by forming the more lipophilic ion-pair with hexadecylphosphate, and from W/O/W microemulsion by dissolving the pentapeptide in the aqueous internal phase. The incorporation of the hydrophilic drug was 5.2% and 1.7% respectively; in both cases, the in vitro release of thymopentin from the solid lipid nanoparticles followed a pseudo-zero-order kinetics.

NMR relaxometric investigations of solid lipid nanoparticles (SLN) containing gadolinium(III) complexes

This work deals with the preparation and relaxometric investigations of solid lipid nanoparticles (SLN) containing [Gd-DTPA(H2O)]2- and [Gd-DOTA(H2O)]-. These paramagnetic chelates are commonly used as contrast agents (CA) for magnetic resonance imaging (MRI) owing to their ability to strongly increase the tissue water proton relaxation rate. The amount of gadolinium(III) (Gd(III)) complex included in the SLN has been evaluated and, on this basis, it has been found that the longitudinal relaxivity of these Gd(III) chelates apparently does not vary, at physiological pH, following their inclusion in SLN. We are unable to establish whether this is due to the free exchange of water from the inner compartment containing the Gd(III) chelate to the bulk water or whether the observed relaxation rate is essentially determined by a fraction of the complex which is close to the surface of the SLN in a region easily accessible to the bulk water. At acidic pH values, the relaxivity of the paramagnetic SLN containing the less thermodynamically and kinetically stable [Gd-DTPA(H2O)]2- markedly increases. This effect may be ascribed to an increased immobilization and/or to an enhanced hydration of the complex on SLN.

Influence of ion pairing on topical delivery of retinoic acid from microemulsions

The purpose of the present study was to determinate the significance of ion pairing on the topical permeation of retinoic acid (R.A) using microemulsions as delivery vehicles. Phenylalanine methyl ester, phenylalanine ethylester, histidine methyl ester, tryptophan methyl ester and valine methyl ester were used as counter ions. Results of diffusion studies through polydimethylsiloxane membrane (PDMS) indicate that retinoic acid permeation from ethanol-pH 6.4 buffer mixture significantly increased in the presence of counter ions. A linear relationship was found between apparent partition coefficients and permeation coefficients. The highest values were with valine methyl ester and phenylalanine ethyl ester. In order to develop alternative formulations for topical administration of R.A, microemulsions were evaluated as delivery vehicles. Oil-in-water (O/W) and water-in-oil (W/O) microemulsion formulations were prepared using water, isopropyl myristate, lecithin, caprylyl-capryl glucoside and ethanol or 1,2 hexanediol. Experiments with PDMS membranes showed decreasing permeabilities of R.A from microemulsions in the presence of counter ions. This was related to the increased lipophilicity and different vehicle membrane affinity of the ion pairs The ability of the systems to deliver R.A through the skin was evaluated in vitro using pig-skin. R.A permeabilities were much lower with microemulsions than with solution, while a large increase in R.A skin deposition was observed only from O/W microemulsions in the presence of counter ions. The depth of skin accumulation was below 100 microm after 24 h application. The results suggest that O/W microemulsions containing a counter ion can be used to optimise drug targeting without a concomitant increase in systemic absorption.

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.

Phase behaviour of microemulsion systems containing lecithin and lysolecithin as surfactants

Abstract Phase diagrams were constructed at 25°C to investigate the phase behaviour of systems containing water, isopropyl myristate, commercially-available soybean lecithin and lysolecithin at different mixing ratios, as surfactant mixture, and alcohol, as cosurfactant. Lysolecithin was obtained by enzymatic hydrolysis from soybean lecithin. The lysolecithin:lecithin mixing ratios were 0.7:1, 1.4:1 and 2.1:1, for the systems containing 1-butanol, and 1.4:1, for the systems containing 1-propanol or ethanol. The surfactant/cosurfactant mixing ratios (Km) were 1/2, 1/1 and 2/1 for 1-butanol, 1/1 and 1/2 for 1-propanol and ethanol. A liquid crystalline region was observed only in systems containing 1-butanol at Km 2/1. The stability range of microemulsions containing lecithin was greatly increased by adding lysolecithin. The extension of the microemulsion domain was very dependent upon the nature of the cosurfactant and on the lysolecithin:lecithin and surfactant/cosurfactant mixing ratios. Infinitely dilutable microemulsions were obtained using 1-propanol or ethanol.

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.

The effect of alcohols with different structures on the formation of warm O/W microemulsions

Abstract The influence of twenty five different alcohols on the formation of warm oil-in-water (O/W) microemulsions was investigated. Selected concentrations of each alcohol were added to fixed amounts of stearic acid, Tween 20 and water at 65 ° C. Fifteen alcohols formed microemulsions, at least at one of the concentrations. A pattern recognition study was performed to elucidate the activities of the alcohols by Principal Component Analysis (PCA). Linear Discriminant Analysis (LDA) was used to classify them. Two classification functions, obtained for alcohols forming / not forming microemulsions, suggest that the formation of warm O/W microemulsion is linked to the nature and the dimension/lipophilicity of the alcohol.