Penetration Profiles Research Articles

A novel tricyclic ligand-containing nonpeptidic HIV-1 protease inhibitor, GRL-0739, effectively inhibits the replication of multidrug-resistant HIV-1 variants and has a desirable central nervous system penetration property in vitro.

We report here that GRL-0739, a novel nonpeptidic HIV-1 protease inhibitor containing a tricycle (cyclohexyl-bis-tetrahydrofuranylurethane [THF]) and a sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC50], 0.0019 to 0.0036 μM), with minimal cytotoxicity (50% cytotoxic concentration [CC50], 21.0 μM). GRL-0739 blocked the infectivity and replication of HIV-1NL4-3 variants selected by concentrations of up to 5 μM ritonavir or atazanavir (EC50, 0.035 to 0.058 μM). GRL-0739 was also highly active against multidrug-resistant clinical HIV-1 variants isolated from patients who no longer responded to existing antiviral regimens after long-term antiretroviral therapy, as well as against the HIV-2ROD variant. The development of resistance against GRL-0739 was substantially delayed compared to that of amprenavir (APV). The effects of the nonspecific binding of human serum proteins on the anti-HIV-1 activity of GRL-0739 were insignificant. In addition, GRL-0739 showed a desirable central nervous system (CNS) penetration property, as assessed using a novel in vitro blood-brain barrier model. Molecular modeling demonstrated that the tricyclic ring and methoxybenzene of GRL-0739 have a larger surface and make greater van der Waals contacts with protease than in the case of darunavir. The present data demonstrate that GRL-0739 has desirable features as a compound with good CNS-penetrating capability for treating patients infected with wild-type and/or multidrug-resistant HIV-1 variants and that the newly generated cyclohexyl-bis-THF moiety with methoxybenzene confers highly desirable anti-HIV-1 potency in the design of novel protease inhibitors with greater CNS penetration profiles.

Dermal Toxicity of Flake-Like α-Alumina Pigments.

Aluminum is one of the most widely used nonferrous metals and an important industrial material, especially for automotive coatings. However, potential toxicity caused by aluminum in humans limits the used of this metal. α-alumina is the most stable form of aluminum in various phases. Although the results of studies evaluating the dermal toxicity of α-alumina remained unclear, this compound can still be used as a pigment in cosmetics for humans. In the current study, we further evaluated the dermal cytotoxic effects of α-alumina on human skin cells and an in vivo mouse model. We also measured the in vitro penetration profile of flake-like α-alumina in porcine skin and assessed the degree of cellular metabolic disorders. Our findings demonstrated that treatment with flake-like α-alumina did not significantly affect cell viability up to 24 h. This compound was found to have a non-penetration profile based on a Franz modified diffusion cell assay. In addition, flake-like α-alumina was not found to induce dermal inflammation as assessed by histology of epidermal architecture, hyperplasia, and the expression of Interleukin-1β and Cyclooxygenase-2. Results of the cellular metabolic disorder assay indicated that flake-like α-alumina does not exert a direct effect on human skin cells. Taken together, our findings provided not only evidence that flake-like α-alumina may serve as a pearlescent pigment in cosmetics but also experimental basis utilizing α-alumina for human application. Our results also obviously provide new insight of the further toxicity study to aluminum based nanoparticles for skin.

Formulation design for topical drug and nanoparticle treatment of skin disease.

The skin has evolved to resist the penetration of foreign substances and particles. Topical therapeutic and cosmeceutical delivery is a growing field founded on selectively overcoming this barrier. Both the biology of the skin and the nature of the formulation/active ingredient must be aligned for efficient transcutaneous delivery. This review discusses the biological changes in the skin barrier that occur with common dermatological conditions. This context is the foundation for the discussion of formulation strategies to improve penetration profiles of common active ingredients in dermatology. Finally, we compare and contrast those approaches to recent advances described in the research literature with an eye toward the future of topical formulation design.

Preclinical to clinical translation of CNS transporter occupancy of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

Background:Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.Methods:We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.Results:TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC50 of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC50 values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [11C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [11C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC50 for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.Conclusions:These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.

Mathematical model of bead profile in high deposition welds

Mathematical models of reinforcement and penetration profile in high deposition welds produced by multiple-wire processes are presented. A practical approach for assessment of shape and size of weld bead is introduced wherein characteristic coefficients (αi) of parametric equations y=f(αi, x) are expressed as functions of process parameters such as welding current, speed, and voltage, and they are determined by calibration of model with experimental observations using a heuristic technique. The validity of new model is demonstrated through a case study presentation on twin-wire welding. Compared to a semi-elliptical reinforcement and a cosine/parabolic penetration profiles in single-wire welds, an elliptical segment and a composite trigonometric function, respectively, are found more appropriate to represent multiple-wire welds. The effects of process parameters on bead profile and weld bead dilution for straight and reverse polarities over a wide range of process parameters are evaluated. The developed models explain effect of welding parameters on weld bead shape and weld cooling time, thus, apt for determining dimensions of heat source in modeling of welding processes.

Indium penetration through thermally grown silicon oxide

Indium penetration through silicon oxide was investigated using thermal oxides capped with polycrystalline silicon. When indium was implanted into the silicon substrate, indium penetrated through a thin oxide into the polycrystalline silicon at low temperatures. The amount of indium penetration was determined by the transient enhance diffusion of indium in silicon. Significant indium penetration was also observed in samples with indium implantation in a thick oxide. The redistribution of indium in the oxide layer controlled the penetration behavior. Such evidence indicates that thermal oxide cannot be used as a diffusion barrier for indium. Diffusion parameters for indium in polycrystalline silicon were extracted according the indium penetration profiles. The activation energy for indium diffusion in polycrystalline silicon is around 2.5 eV, which is lower than that in silicon. However, the indium diffusion in polycrystalline silicon was reduced when the thermal oxide under the polycrystalline silicon layer became thicker.

Polymeric Nanocapsules and Lipid-Core Nanocapsules Have Diverse Skin Penetration.

Biodegradable nanoparticles have been widely studied as drug carriers in order to increase drug solubility in aqueous media, modify biodistribution, target tissues and organs or control the drug release. Those nanoparticles are, in general, produced as liquid formulations to act as final dosage forms or as intermediate for solid or semi-solid products. Considering the dermatological applications, as medicines or cosmetics, different nanoparticles have been proposed to control the skin penetration of encapsulated lipophilic substances. A point rarely investigated is the penetration of the carrier itself into the skin, independent of the drug penetration profile. In this way, our objective was to correlate the flexibility of the biodegradable nanoparticles to the depth of their skin penetration. To minimize the impact of the chemical composition, the surface chemistry or the shape and size distribution on the results, two kinds of polymeric nanocapsules presenting diverse mechanical properties were produced using almost the same materials and their concentrations. The nanocapsules (NC) and the lipid-core nanocapsules (LNC) were prepared by solvent displacement using Rhodamine B-labeled polymer, oil and surfactants. The only difference in composition between them is the presence of sorbitan monostearate in the latter which was used to have a more rigid nanoparticle as previously reported. NC and LNC had, respectively, mean diameters of 178 and 180 nm and zeta potentials of -11 and -9 mV. The in vitro skin penetration was carried out using Franz cells (pig skin as membrane). Skin samples were observed by confocal laser scanning microscopy (CLSM). NC reached the dermis, while LNC was retained at the outermost layers of the skin. The result was in accordance with the flexibility previously determined for those nanocapsules, in a way that higher flexibility gives deeper penetration. NC can reach the dermis and LNC can act as reservoir systems at the epidermis.

Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study

Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non-aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS(®) with diclofenac emulgel. A 200 mg of diclofenac from either Dynapar QPS(®) (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and Kel, of diclofenac were determined for both the formulations. Mean Cmax after administration of Dynapar QPS(®) and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0-t and AUC0-∞ after administration of Dynapar QPS(®) was higher as compared to diclofenac emulgel (AUC0-t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-∞: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS(®) as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients.

In Vitro Liberation of Indomethacin from Chitosan Gels Containing Microemulsion in Different Dissolution Mediums

The objective of this research is to outline the liberation of indomethacin from different chitosan gels containing O/W microemulsion. The influence of surfactant, sodium lauryl sulfate, in two concentrations (0.5% and 0.75%, w/w) was determined in dissolution medium on the release of indomethacin, which was used as poor water-soluble model drug. Chitosan gels were prepared in four different concentrations of chitosan-1%, 1.5%, 2%, and 3% (w/w). Microemulsion enhanced the liberation of the indomethacin from chitosan gels into all dissolution mediums. Adding the surfactant into phosphate-buffered saline decreased the amount of liberated indomethacin from microemulsion, gel mixture, but increased the drug liberation from pure chitosan gels. It was detected that with the increased concentration of chitosan in the samples, the amount of indomethacin liberated (p < 0.05) also increased. A conclusion was drawn that the liberation of indomethacin from chitosan gels was influenced by increased pH of the samples. The high viscosity induced a higher release of indomethacin from 3% (w/w) chitosan hydrogel at pH 5.8 as compared with 3% (w/w) chitosan hydrogel at pH 3.8. The highest percentage of released indomethacin was determined when a mixture of microemulsion gel with higher chitosan content was used.

A Simplified Approach for Estimating Skin Permeation Parameters from In Vitro Finite Dose Absorption Studies

Historically, percutaneous absorption permeation parameters have been derived from in vitro infinite dose studies, yet there is uncertainty in their accuracy if the applied vehicle saturates or damages the stratum corneum, or when the permeation parameters are inappropriately derived from cumulative absorption data. An approach is provided for determining penetration parameters from in vitro finite dose data. Key variables, and equations for their derivation, are identified from the literature and provide permeation parameters that use only Tmax , AUC, and AUMC from finite dose data. The equations are tested with computer-generated model data and to actual study data. Derived permeation parameters obtained from the computer model data match those used in generating the simulated finite dose data. Parameters obtained from actual study data reasonably and acceptably model the penetration profile kinetics of the study data. From in vitro finite dose absorption data, three parameters can be obtained: the diffusion transit time (td ), which characterizes the diffusion coefficient, the partition volume (Vm P), which characterizes the partition coefficient, and the permeation coefficient (Kp ). These parameters can be obtained from finite dose data without having to know the length of the diffusion pathway through the membrane.

Grain size dependence of penetration depth of hydrogen injection into polycrystalline graphite by molecular simulation

Many different carbon materials are developed for diverse applications for industrial and scientific uses. It is known that the amount of hydrogen retained in carbon materials under plasma irradiation strongly depends on the structural characteristics of the material, such as grain size. To clarify the cause of the difference in the amount of hydrogen retained in different carbon materials, hydrogen atom injection into polycrystalline graphite is investigated on the atomic scale by a hybrid simulation technique consisting of binary-collision-approximation-based simulation and molecular dynamics simulation. Then, the incident energy and grain size dependences of the penetration profile of incident hydrogen atoms are carefully investigated.

Impurity Diffusion in Highly-Ordered Intermetallic Compounds Studied by Nuclear Quadrupole Interactions

Diffusion of impurity atoms depends on the sublattices occupied, active diffusion mechanisms, and jump frequencies to neighboring sites. The method of perturbed angular correlation of gamma rays (PAC) has been applied over the past decade to study impurity diffusion through measurement of nuclear quadrupole interactions (NQI) at nuclei of 111In/Cd probe atoms. Extensive measurements have been made on highly-ordered compounds having the L12 crystal structure, including In3R, Sn3R, Ga3R, Al3R and Pd3R phases (R= rare-earth element). Measurements in thermal equilibrium at high temperature served to determine lattice locations of 111In parent probe-atoms, through characteristic NQIs, and to measure diffusional jump-frequencies of 111Cd daughter probe-atoms, through relaxation of the NQI. This paper summarizes results of the jump-frequency measurements and relates them to the conventional diffusivity that can be determined, for example, from penetration profiles of tracer species. In spite of chemical similarities of the series of rare-earth phases studied, remarkably large variations in jump frequencies have been observed especially along series of In3R and Pd3R phases. Most phases appear as “line compounds” in binary phase diagrams, but large differences in site-preferences and jump-frequencies were observed for samples prepared to have the opposing limiting phase boundary compositions. Comparisons of jump-frequencies measured at opposing boundary compositions can give insight into the predominant microscopic diffusional mechanisms of the impurity. A change in diffusion mechanism was proposed in 2009 to explain jump-frequency systematics for In3R phases. An alternative explanation is proposed in the present paper based on site-preferences of 111Cd daughter probes newly observed along the parallel Pd3R series. The diffusivity can be expressed as the product of a jump-frequency such as measured in these studies and a correlation factor for diffusion that depends on the diffusion mechanism. The correlation factor can be modeled for the L12 structure and diffusion sublattice of interest using a five-frequency model originally proposed for metals. Although the correlation factor is an essential parameter for the diffusion of impurities, it has never been measured. It is suggested that values of the correlation factor can be determined feasibly by combining results of jump-frequency measurements such as the present ones with diffusivity measurements made for the same host-impurity systems.

Determination of in vitro usnic acid delivery into porcine skin using a HPLC method.

Usnic acid, a lichen metabolite, has been proposed as a potential topical treatment for microbial skin lesions, burn wounds as well as a sunscreen. An isocratic HPLC method was validated according to FDA's Guidance for Industry: Bioanalytical Method Validation to determine skin penetration and permeation of usnic acid. The penetration and permeation of usnic acid was evaluated using Franz cells and porcine skin. The method was valid according to selectivity, linearity, precision, accuracy and stability. Usnic acid was quantified in the skin surface (6.13 µg cm(2)), stratum corneum (34.4 µg cm(2)), viable epidermis (5.6 µg cm(2)), dermis (28.2 µg cm(2)) and receptor compartment (3.2 µg cm(2)). These results help us to understand the penetration profile of usnic acid and plan topical therapeutic approaches as well as new topical delivery systems to modulate this penetration profile.

Quantitative estimation of carbonation and chloride penetration in reinforced concrete by laser-induced breakdown spectroscopy

The penetration profile of chlorine in a reinforced concrete (RC) specimen was determined by laser-induced breakdown spectroscopy (LIBS). The concrete core was prepared from RC beams with cracking damage induced by bending load and salt water spraying. LIBS was performed using a specimen that was obtained by splitting the concrete core, and the line scan of laser pulses gave the two-dimensional emission intensity profiles of 100×80mm2 within one hour. The two-dimensional profile of the emission intensity suggests that the presence of the crack had less effect on the emission intensity when the measurement interval was larger than the crack width. The chlorine emission spectrum was measured without using the buffer gas, which is usually used for chlorine measurement, by collinear double-pulse LIBS. The apparent diffusion coefficient, which is one of the most important parameters for chloride penetration in concrete, was estimated using the depth profile of chlorine emission intensity and Fick's law. The carbonation depth was estimated on the basis of the relationship between carbon and calcium emission intensities. When the carbon emission intensity was statistically higher than the calcium emission intensity at the measurement point, we determined that the point was carbonated. The estimation results were consistent with the spraying test results using phenolphthalein solution. These results suggest that the quantitative estimation by LIBS of carbonation depth and chloride penetration can be performed simultaneously.

Influence of Heat Input in Automatic GMAW: Penetration Prediction and Microstructural Observation

In the present work, the influence of heat input is studied on depth of penetration while depositing bead on AISI 304 stainless steel using an indigenously fabricated automatic gas metal arc welding (GMAW) movement setup. Depth of penetration and fusion zone profiles are predicted at different conditions by the bond graph modeling approach and validated using measured depth of penetration and fusion profile. The effects of heat input on toughness and metallurgical behavior are analyzed while joining AISI 304 plates using automatic GMAW. Heat input and gas flow rate significantly influence the toughness at room temperature and at −20°C. Metallurgical observations by scanning electron microscopy are carried out and it is observed that high heat input and lower cooling rate increase grain size. High heat input and rapid cooling prevent grain growth and lead to grain refinement.

Water Penetration Profile at the Protein-Lipid Interface in Na,K-ATPase Membranes

The affinity of ionized fatty acids for the Na,K-ATPase is used to determine the transmembrane profile of water penetration at the protein-lipid interface. The standardized intensity of the electron spin echo envelope modulation (ESEEM) from 2H-hyperfine interaction with D2O is determined for stearic acid, n-SASL, spin-labeled systematically at the C-n atoms throughout the chain. In both native Na,K-ATPase membranes from shark salt gland and bilayers of the extracted membrane lipids, the D2O-ESEEM intensities of fully charged n-SASL decrease progressively with position down the fatty acid chain toward the terminal methyl group. Whereas the D2O intensities decrease sharply at the n = 9 position in the lipid bilayers, a much broader transition region in the range n = 6 to 10 is found with Na,K-ATPase membranes. Correction for the bilayer population in the membranes yields the intrinsic D2O-intensity profile at the protein-lipid interface. For positions at either end of the chains, the D2O concentrations at the protein interface are greater than in the lipid bilayer, and the positional profile is much broader. This reveals the higher polarity, and consequently higher intramembrane water concentration, at the protein-lipid interface. In particular, there is a significant water concentration adjacent to the protein at the membrane midplane, unlike the situation in the bilayer regions of this cholesterol-rich membrane. Experiments with protonated fatty acid and phosphatidylcholine spin labels, both of which have a considerably lower affinity for the Na,K-ATPase, confirm these results.

Determination of the Corrosion Probability in Reinforced Concrete Structures by Design in Situ Monitoring System

Introduction Corrosion of concrete rebar has been established as the main factor of the premature deterioration of reinforced concrete structures. The occurrence of such phenomena represents mostly the durability problems of the material, especially when the structure is subjected to the chloride ions presence (in marine or high salinity enviroment) and large amounts of carbon dioxide (CO2 ), processes known as chloride penetration and carbonation respectively[1,2,3]. Once the corrosión process has appeared in rebar, these begin to generate large stresses on the layer of concrete around them (due to the iron oxides that accumulate around the transversal area) which over time can generate microcracks, cracks and failure on the general structure[4].Given the importance of preserving civil structures, is evident the strong necessity of obtaining a system with great flexibility to perform the estimation in situ of the corrosive state, capable to dispose the information for immediate consultation anywhere with minimum internet access. Therefore, the present work shows the development and implementation of a system for in situ monitoring of corrosion, for any reinforced concrete structure based on ASTM C876-91[5] standard for measuring half-cell potential, with which it is possible to determine the corrosion probability of rebar in reinforced concrete structures. Also, the equipment performance is presented by using different reference electrodes as Copper / Copper Sulfate (Cu -CuSO4 ), silver / silver chloride (Ag / AgCl) and Zinc / Zinc Sulfate (Zn -ZnSO4 ). Experiments and Results It was obtained a system for in situ monitoring of corrosion for reinforced concrete, that allows to estimate the corrosion probability on rebar, where the user send a text message, to start the test in the system and in return, via GPRS (General Packet Radio Service), the equipment disposes the data trend on a graphic trough a web server on an internet domain (figure 1). The system was tested on a building of the University complex, where its performance was evaluated using three different reference electrodes, obtaining an error over the measurement, between the standard and the system, of 6.62% (figure 2). References (1) ROA-RODRIGUEZ, G., APERADOR, W., DELGADO, A. Calculation of Chloride Penetration Profile in Concrete Structures. International Journal of Electrochemical Science. v. 8, p. 5022-5035, Apr. 2013 (2) HA WONG, S., VELI, S. Corrosion Monitoring of Reinforced Concrete Structures - A Review. International Journal of Electrochemistry Science, v. 2, p. 1 – 28, Jan. 2007. (3) SATHIYANARAYANAN, S., PANJALI NATARAJAN, K., SARAVANAN, S., SRINIVASAN, G. Corrosion monitoring of steel in concrete by galvanostatic pulse technique. Cement & Concrete Composites, v. 28, p. 630-637, May. 2006. (4) SHAMSAD, A., Reinforcement corrosion in concrete structures, its monitoring and service life prediction––a review. Cement & Concrete Composites, v. 25, p. 459 – 471, May. 2003 (5) ASTM Standard C876-09, 1991, Standard Test Method for Corrosion Potentials of Uncoated Reinforcing Steel in Concrete. ASTM International, West Conshohocken, PA, 2003, DOI: 10.1520/C0876-09.

Gaussian-function-based deconvolution method to determine the penetration ability of petrolatum oil into in vivo human skin using confocal Raman microscopy

Human skin pre-treated with petrolatum was analyzed in vivo using confocal Raman microscopy in order to determine the penetration depth of the oil into the skin. The broad Raman peak (2820–3030 cm−1) measured in vivo on human skin in the high wavenumber region exhibits two prominent main Raman peaks at 2880 cm−1 and 2935 cm−1 that originated from cutaneous lipids and keratin and two main peak shoulders at 2850 cm−1 and 2980 cm−1 that originated from lipids and keratin, respectively. Topical application of petrolatum oil onto the skin gives rise to an increase of the intensity of the broad lipid–keratin Raman peak (2820–3030 cm−1). Herewith, not only the intensity of the lipid part but also of the keratin part is increased, making the normalization to keratin and the determination of the petrolatum penetration profile erroneous. To solve this problem, the Gaussian-function-based deconvolution method is introduced in analyzing the Raman spectrum of the lipid–keratin peak and the least square method is applied for analyzing the petrolatum penetration profile. Results obtained in vivo show that the petrolatum oil does not penetrate deeper than 10 µm into intact human skin.

Antioxidative effects and percutaneous absorption of five polyphenols

A new strategy was designed to evaluate the antioxidant effectiveness of five topically applied polyphenols following skin penetration profiles. The antioxidants were the following polyphenol derivatives: epicatechin, resveratrol, rutin, quercetin, and trolox, which was used as the reference antioxidant. The hydrophilic/lipophilic character of these compounds was evaluated, and their antioxidant activity was measured by the DPPH method. The percutaneous absorption of these polyphenols was obtained by an in vitro methodology using porcine skin biopsies. This methodology involves the quantification of the antioxidants present in each specific skin layer to evaluate antioxidant effectiveness. The antioxidant activity in each skin layer was also determined by the DPPH method. The results indicated that lipophilic antioxidants (epicatechin, resveratrol, quercetin, and trolox) penetrated deeper into the skin layers, whereas a more hydrophilic compound, rutin, remained on the skin surface. The antioxidant evaluation of each skin compartment suggested that resveratrol and rutin were the most effective topically applied compounds in view of their antioxidant activity and their skin penetration profile.

Alpha and deuteron irradiation effects on silica nanoparticles

We present an experimental investigation focused on the effects of alpha and deuteron irradiation on different silica nanoparticles. The study has been devoted also to characterize the induced point defects and the eventual structural modifications to evaluate the effects of the different irradiation source in comparison with the bulk materials. After irradiation up to about 1016 ions cm−2, we performed electron paramagnetic resonance (EPR), photoluminescence (PL), infrared (IR) absorption, Raman, and atomic force microscopy (AFM) measurements. We found that the two types of irradiation qualitatively induce comparable effects. Furthermore, irradiation generates the so-called twofold coordinated Si and the H(I) point defects, originating from the reaction of the former with hydrogen atoms. The occurrence of these defects is a not trivial and interesting finding due to its connection to irradiation-induced oxygen deficiency, not yet evidenced by other irradiation of silica nanoparticles. We also detected the E′Si paramagnetic centers and found that their lineshape at the highest fluence, independently from the nanoparticles size and irradiation source, is different from the one observed in the bulk. Furthermore, the integral of the E′Si signal does not depend significantly on the nanoparticles size differing from previous irradiation with β-ray of the same nanoparticles. AFM images indicate the absence of significant radiation induced sintering between the nanoparticles in the plan orthogonal to the irradiation direction suggesting the absence of morphological changes, whereas IR measurements suggest the occurrence of some structural modifications in all the nanoparticles, which consist in the decrease of the peak value of the Si–O–Si angle distribution. Finally, irradiation effects are induced not uniformly along the irradiation direction, as supported also by micro-Raman investigation of an irradiated bulk silica material and simulations of ions penetration profiles. These results suggest the occurrence of some irradiation effects due to light ion bombardment specific of nanoparticles.