Penetration of sweet cherry skin by 45Ca-salts: pathways and factors

Calcium is beneficial to sweet cherry physiology. The objective was to investigate factors affecting uptake of Ca into mature sweet cherry fruit through their skins. Penetration of 45Ca-salts was monitored using whole fruit or excised fruit skins mounted in diffusion cells. Penetration of 45CaCl2 into intact fruit and through excised skins increased with time. Sealing the pedicel/fruit junction decreased penetration, but sealing the stylar scar had no effect. There was little difference in permeances of the fruit skin to 45CaCl2, 45Ca(NO3)2, 45Ca-formate, 45Ca-acetate, 45Ca-lactate or 45Ca-propionate. Only 45Ca-heptagluconate penetrated at a slower rate. Increasing temperature markedly increased Ca-penetration. Penetration was most rapid at 35 °C, intermediate at 22 °C and slowest at 12 °C. Increasing relative humidity (RH) from 0, 28, 75 to 100% increased penetration of 45CaCl2, but penetration of 45Ca-formate was restricted to 100% RH. Increasing the RH from 50 to 100% at 96 h after droplet application had no effect on penetration of 45CaCl2, but increased penetration of 45Ca-formate. The results reveal that: (1) the fruit/pedicel junction is a site of preferential Ca-uptake and (2) Ca-penetration is limited by the mobility of the Ca ion in the dried-down droplet residue when the point of deliquescence of the applied salt exceeds the ambient RH.

Antioxidant-Loaded Mucoadhesive Nanoparticles for Eye Drug Delivery: A New Strategy to Reduce Oxidative Stress

There are several approaches to treat ocular diseases, which can be invasive or non-invasive. Within the non-invasive, new pharmaceutical strategies based on nanotechnology and mucoadhesive polymers are emerging methodologies, which aim to reach an efficient treatment of eye diseases. The aim of this work was the development of novel chitosan/hyaluronic acid nanoparticle systems with mucoadhesive properties, intended to encapsulate antioxidant molecules (e.g., crocin) aiming to reduce eye oxidative stress and, consequently, ocular disease. An ultraviolet (UV) absorber molecule, actinoquinol, was also added to the nanoparticles, to further decrease oxidative stress. The developed nanoparticles were characterized and the results showed a mean particle size lower than 400 nm, polydispersity index of 0.220 ± 0.034, positive zeta potential, and high yield. The nanoparticles were also characterized in terms of pH, osmolality, and viscosity. Mucoadhesion studies involving the determination of zeta potential, viscosity, and tackiness, showed a strong interaction between the nanoparticles and mucin. In vitro release studies using synthetic membranes in Franz diffusion cells were conducted to unravel the drug release kinetic profile. Ex vitro studies using pig eye scleras in Franz diffusion cells were performed to evaluate the permeation of the nanoparticles. Furthermore, in vitro assays using the ARPE-19 (adult retinal pigment epithelium) cell line showed that the nanoparticles can efficiently decrease oxidative stress and showed low cytotoxicity. Thus, the developed chitosan/hyaluronic acid nanoparticles are a promising system for the delivery of antioxidants to the eye, by increasing their residence time and controlling their delivery.

Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device

The efficacy of transdermal absorption of drugs and the irritation or corrosion potential of topically applied formulations are important areas of investigation in pharmaceutical, military and cosmetic research. The aim of the present experiments is to test the role of P-glycoprotein in dermal drug delivery in various ex vivo and in vitro platforms, including a novel microchip technology developed by Pázmány Péter Catholic University. A further question is whether the freezing of excised skin and age have any influence on P-glycoprotein-mediated dermal drug absorption. Two P-glycoprotein substrate model drugs (quinidine and erythromycin) were investigated via topical administration in diffusion cells, a skin-on-a-chip device and transdermal microdialysis in rat skin. The transdermal absorption of both model drugs was reduced by P-glycoprotein inhibition, and both aging and freezing increased the permeability of the tissues. Based on our findings, it is concluded that the process of freezing leads to reduced function of efflux transporters, and increases the porosity of skin. P-glycoprotein has an absorptive orientation in the skin, and topical inhibitors can modify its action. The defensive role of the skin seems to be diminished in aged individuals, partly due to reduced thickness of the dermis. The novel microfluidic microchip seems to be an appropriate tool to investigate dermal drug delivery.

Formulation and In-Vitro Penetration Test of Ketoconazole Nanoemulsion

This study was aimed to formulate ketoconazole into nanoemulsion form and to compared the penetration ability of each formula with ketoconazole cream on the market as control. Formulation of nanoemulsion uses spontaneous methods and and also measurement of particle using the Particle Size Analyzer (PSA). In vitro penetration test used Franz diffusion cells. The results showed that nanoemulsion of each formula had different particle sizes, it was due to the distress of homogenizing two different systems, the duration and speed of stirring also affect the homogenity. The higher concentration of surfactant (tween 80) in the nanoemulation preparation could increasing the penetration ability of the preparation, but if the concentration exceeds the critical micelle concentration (CMC), a tight surfactant matrix (tween 80) will be formed which causes the release of ketoconazole to be slowed. Based on the observation, the highest penetration test was formula F3 as many as 4,268.01 µg/cm.

A Case Study of Brass Foundry Workers’ Estimated Lead (Pb) Body Burden from Different Exposure Routes

Objectives The most pronounced occupational exposure routes for lead (Pb) are inhalation and gastrointestinal uptake mainly through hand-to-mouth behaviour. Skin absorption has been demonstrated for organic Pb compounds, but less is known about inorganic Pb species. Several legislative bodies in Europe are currently proposing lowering biological exposure limit values and air exposure limits due to new evidence on cardiovascular effects at very low blood Pb levels. In light of this, all exposure routes in occupational settings should be revisited to evaluate how to lower the overall exposure to Pb. Methods The aim of the study was to investigate the possible exposure routes in workers operating computer numerical control-machines in a brass foundry and specifically to understand if metal cutting fluids (MCFs) used by the workers could lead to skin absorption of Pb. The different bronze alloys at the facility may contain up to 20% Pb. After obtaining written informed consent from the workers (n = 7), blood, skin wipes, and personal air samples were collected. In addition, MCFs used on the day of exposure measurements were collected for in vitro skin absorption studies using stillborn piglet skin mounted in static Franz diffusion cells (n = 48). All samples were analysed for Pb content using inductively coupled plasma mass spectrometry. Results Pb air concentration (<0.1–3.4 µg m−3) was well below the Swedish occupational exposure limit value. Blood Pb was in the range of <0.72–33 µg dl−1, and Pb on skin surfaces, after performing normal work tasks during 2 h, was in the range of 0.2–48 µg cm−2. Using the MCFs in diffusion cells showed that skin absorption had occurred at very low doses, and that up to 10% of the Pb content was present in the skin after 24 h exposure. Using these results in the US EPA adult lead model, we could estimate a contribution to blood Pb from the three exposure routes; where hand-to-mouth behaviour yielded the highest contribution (16 µg Pb dl−1 blood), followed by skin absorption (3.3–6.3 µg Pb dl−1 blood) and inhalation (2.0 µg Pb dl−1 blood). Conclusions This case study shows that MCF may lead to skin absorption of inorganic Pb and contribute to a systemic dose (quasi-steady state). Furthermore, even though good hand hygienic measures were in place, the workers’ skin exposure to Pb is in all likelihood an important contributor in elevating blood Pb levels. Skin exposure should thus be monitored routinely in workers at facilities handling Pb, to help reducing unnecessary occupational exposure.

Validation of an Ex Vivo Permeation Method for the Intestinal Permeability of Different BCS Drugs and Its Correlation with Caco-2 In Vitro Experiments

The absorption study of drugs through different biological membranes constitutes an essential step in the development of new pharmaceutical dosage forms. Concerning orally administered forms, methods based on monolayer cell culture of Caco-2 (Caucasian colon adenocarcinoma) have been developed to emulate intestinal mucosa in permeability studies. Although it is widely accepted, it has disadvantages, such as high costs or high technical complexity, and limitations related to the simplified structure of the monolayer or the class of molecules that can be permeated according to the transport mechanisms. The aim of this work was to develop a new ex vivo methodology which allows the evaluation of the intestinal apparent permeability coefficient (Papp) while using fewer resources and to assess the correlation with Caco-2. To this end, pig (Sus scrofa) duodenum segments were mounted in Franz diffusion cells and used to permeate four different drugs: ketorolac tromethamine (Kt), melatonin (Mel), hydrochlorothiazide (Htz), and furosemide (Fur). No statistically significant differences (p > 0.05) were observed corelating Papp values from Franz diffusion cells and Caco-2 cell experiments for Kt, Htz, and Fur. However, there were statistically significant differences (p < 0.05) correlating Papp values and Mel. The difference is explained by the role of Mel in the duodenal epithelial paracellular permeability reduction. Ex vivo permeation may be an equivalent method to Caco-2 for drugs that do not produce intestinal membrane phenomena that could affect absorption.