Results from an extended study on the reliability of a questionnaire for the diagnosis of sensitive skin: Confirmations and improvements

ObjectiveA recently proposed self-assessment questionnaire aimed at diagnosing sensitive skin provided promising results in a relatively small population. The main objectives were: (i) to assess the reliability of the aforementioned questionnaire in a larger population and verify the cut-off score previously found to predict skin sensitivity (defined as positivity to LAST, lactic acid stinging test) and (ii) to define a formula that yields the probability of a positive LAST result. MethodsAdult volunteers were included in this observational, cross-sectional, extended study. Both LAST-positive subjects, who were considered as having sensitive skin ('patients') and negative ones ('controls') completed the questionnaire, which concerned sensitivity to possible triggers of unpleasant skin sensations in real life. A cumulative score (questionnaire-based skin sensitivity score, 0-10) was calculated from the sum of all items. ResultsThree hundred and sixty-four subjects were enrolled, 214 patients and 150 controls. The mean questionnaire-based skin sensitivity score was significantly higher among patients than controls. Using two different methods, cut-off values of 4 and 5 were defined for the identification of LAST-positive subjects, with 76.6% and 72.8% accuracy, respectively. Scores below 4 or above 5 showed a high (80% or better) negative or positive predictive value, respectively. The coefficients found that in multivariate analysis for each questionnaire item, gender and age allowed us to calculate the probability of LAST positivity with higher precision taking into account the 'relative weight' of each factor. ConclusionWith small variations in the results, the self-assessment questionnaire confirmed its reliability for diagnosing sensitive skin in clinical practice

Niosomes for Topical Application of Antioxidant Molecules: Design and In Vitro Behavior

In the present study, gels based on xanthan gum and poloxamer 407 have been developed and characterized in order to convey natural antioxidant molecules included in niosomes. Specifically, the studies were conducted to evaluate how the vesicular systems affect the release of the active ingredient and which formulation is most suitable for cutaneous application. Niosomes, composed of Span 20 or Tween 20, were produced through the direct hydration method, and therefore, borate buffer or a micellar solution of poloxamer 188 was used as the aqueous phase. The niosomes were firstly characterized in terms of morphology, dimensional and encapsulation stability. Afterwards, gels based on poloxamer 407 or xanthan gum were compared in terms of spreadability and adhesiveness. It was found to have greater spreadability for gels based on poloxamer 407 and 100% adhesiveness for those based on xanthan gum. The in vitro diffusion of drugs studied using Franz cells associated with membranes of mixed cellulose esters showed that the use of a poloxamer micellar hydration phase determined a lower release as well as the use of Span 20. The thickened niosomes ensured controlled diffusion of the antioxidant molecules. Lastly, the in vivo irritation test confirmed the safeness of niosomal gels after cutaneous application

The Potential of Caffeic Acid Lipid Nanoparticulate Systems for Skin Application : In Vitro Assays to Assess Delivery and Antioxidant Effect

The object of this study is a comparison between solid lipid nanoparticles and ethosomes for caffeic acid delivery through the skin. Caffeic acid is a potent antioxidant molecule whose cutaneous administration is hampered by its low solubility and scarce stability. In order to improve its therapeutic potential, caffeic acid has been encapsulated within solid lipid nanoparticles and ethosomes. The effect of lipid matrix has been evaluated on the morphology and size distribution of solid lipid nanoparticles and ethosomes loaded with caffeic acid. Particularly, morphology has been investigated by cryogenic transmission electron microscopy and small angle X-ray scattering, while mean diameters have been evaluated by photon correlation spectroscopy. The antioxidant power has been evaluated by the 2,2-diphenyl-1-picrylhydrazyl methodology. The influence of the type of nanoparticulate system on caffeic acid diffusion has been evaluated by Franz cells associated to the nylon membrane, while to evaluate caffeic acid permeation through the skin, an amperometric study has been conducted, which was based on a porcine skin-covered oxygen electrode. This apparatus allows measuring the O2 concentration changes in the membrane induced by polyphenols and H2O2 reaction in the skin. The antioxidative reactions in the skin induced by caffeic acid administered by solid lipid nanoparticles or ethosomes have been evaluated. Franz cell results indicated that caffeic acid diffusion from ethosomes was 18-fold slower with respect to solid lipid nanoparticles. The amperometric method evidenced the transdermal delivery effect of ethosome, indicating an intense antioxidant activity of caffeic acid and a very low response in the case of SLN. Finally, an irritation patch test conducted on 20 human volunteers demonstrated that both ethosomes and solid lipid nanoparticles can be safely applied on the skin

Dimethyl Fumarate-Loaded Transethosomes: A Formulative Study and Preliminary Ex Vivo and In Vivo Evaluation

In this study, transethosomes were investigated as potential delivery systems for dimethyl fumarate. A formulative study was performed investigating the effect of the composition of transethosomes on the morphology and size of vesicles, as well as drug entrapment capacity, using cryogenic transmission electron microscopy, photon correlation spectroscopy, and HPLC. The stability of vesicles was evaluated, both for size increase and capability to control the drug degradation. Drug release kinetics and permeability profiles were evaluated in vitro using Franz cells, associated with different synthetic membranes. The in vitro viability, as well as the capacity to improve wound healing, were evaluated in human keratinocytes. Transmission electron microscopy enabled the evaluation of transethosome uptake and intracellular fate. Based on the obtained results, a transethosome gel was further formulated for the cutaneous application of dimethyl fumarate, the safety of which was evaluated in vivo with a patch test. It was found that the phosphatidylcholine concentration affected vesicle size and lamellarity, influencing the capacity to control dimethyl fumarate's chemical stability and release kinetics. Indeed, phosphatidylcholine 2.7% w/w led to multivesicular vesicles with 344 nm mean size, controlling the drug's chemical stability for at least 90 days. Conversely, phosphatidylcholine 0.9% w/w resulted in 130 nm sized unilamellar vesicles, which maintained 55% of the drug over 3 months. These latest kinds of transethosomes were able to improve wound healing in vitro and were easily internalised by keratinocytes. The selected transethosome gel, loading 25 mg/mL dimethyl fumarate, was not irritant after cutaneous application under occlusion, suggesting its possible suitability in the treatment of wounds caused by diabetes mellitus or peripheral vascular diseases

Ethosomal Gel for Topical Administration of Dimethyl Fumarate in the Treatment of HSV-1 Infections

The infections caused by the HSV-1 virus induce lesions on the lips, mouth, face, and eye. In this study, an ethosome gel loaded with dimethyl fumarate was investigated as a possible approach to treat HSV-1 infections. A formulative study was conducted, evaluating the effect of drug concentration on size distribution and dimensional stability of ethosomes by photon correlation spectroscopy. Ethosome morphology was investigated by cryogenic transmission electron microscopy, while the interaction between dimethyl fumarate and vesicles, and the drug entrapment capacity were respectively evaluated by FTIR and HPLC. To favor the topical application of ethosomes on mucosa and skin, different semisolid forms, based on xanthan gum or poloxamer 407, were designed and compared for spreadability and leakage. Dimethyl fumarate release and diffusion kinetics were evaluated in vitro by Franz cells. The antiviral activity against HSV-1 was tested by plaque reduction assay in Vero and HRPE monolayer cells, while skin irritation effect was evaluated by patch test on 20 healthy volunteers. The lower drug concentration was selected, resulting in smaller and longer stable vesicles, mainly characterized by a multilamellar organization. Dimethyl fumarate entrapment in ethosome was 91% w/w, suggesting an almost total recovery of the drug in the lipid phase. Xanthan gum 0.5%, selected to thicken the ethosome dispersion, allowed to control drug release and diffusion. The antiviral effect of dimethyl fumarate loaded in ethosome gel was demonstrated by a reduction in viral growth both 1 h and 4 h post-infection. Moreover, the patch test demonstrated the safety of the ethosomal gel applied on the skin