Permeability

The OECD guideline for studies on percutaneous penetration to be used in hazard and risk evaluations prescribes experimental conditions with optimal barrier integrity of the skin, which in many occupational settings probably is not true. Thus, workers may have compromised skin due to chemical or mechanical damage, due to different medical conditions (eczema, dermatitis, skin irritation) or related to occupational scenarios involving prolonged wet work. The present study used the OECD guideline procedures to study the in vitro percutaneous penetration through human skin of a number of model substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present study demonstrates that a limited damage to the skin significantly increases the permeability coefficient (K p) as well as total percutaneous penetration of chemicals, and most significantly for those compounds that due to their physicochemical characteristics (the most hydrophilic as well as the most lipophilic) have low penetration rates through intact skin. The present experiment not only confirms the proportionality between lipophilicity and potential for percutaneous penetration, but also illustrates that at a certain degree of lipophilicity of a model compound, the different skin compartments become more attractive for temporary deposition of model compounds. Moreover, a clear change from epidermal deposition towards a dominating dermis deposition of chemicals temporarily deposited within the skin is seen following damage to the skin barrier. Thus, the distribution of chemicals within the skin compartments is affected by the physicochemical characteristics of the chemicals as well as by the integrity of the skin. This observation may have implications when evaluating the possibility of removing chemicals from the skin through different cleansing procedures following unintended dermal exposures.

A diffusion model is presented to account for the disposition of chemicals applied to skin as transient exposures. Two conditions are considered that apply to the skin surface following the exposure period, which are applicable to chemicals exhibiting two extremes of chemical volatility. For one case, representing highly volatile compounds, the solution is generalized to apply to multiple transient exposures. For both cases, algebraic expressions are derived to calculate the total amount of chemical that penetrates the skin. The theory is applied to experimental measurements of the in vitro penetration of diethyl phthalate applied to hairless guinea pig (HGP) skin and silicone rubber membranes (SRMs) as transient exposures. The transient exposure theory ably models the experimental data, with coefficients of determination greater than 0.97 (HGP) and greater than 0.99 (SRM). The ability of parameters derived from concurrent infinite dose experiments to predict the time course of absorption from transient exposures is explored. Discrepancies were found between measured cumulative penetration of chemical from transient exposure experiments and penetration predicted from parameters derived from infinite dose experiments, particularly for HGP. Possible reasons are explored. The current model may provide a realistic framework for estimating absorption from occupational, environmental and pharmaceutical dermal exposures. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1578–1592, 2008

The thick film NixZn(1−x)Fe2O4 on alumina substrate was prepared by screen printing of the ferrite powder synthesized by chemical co-precipitation method using nitrate precursors. These NixZn(1−x)Fe2O4 thick films of varying x were characterized by X-ray diffraction, FTIR spectroscopy and SEM (scanning electron microscopy). The permittivity and permeability were measured by overlay technique. Voltage standing wave ratio method was also used to measure the dielectric constant. The permittivity was found to increase with Ni content varying between 13 and 18. The permeability was ∼3.01. The overlay technique provides an easy method for measurement of permittivity and permeability of ferrite thick film.

The Vapor Extraction (VAPEX) process, a newly developed Enhanced Oil Recovery (EOR) process to recover heavy oil and bitumen, has been studied theoretically and experimentally and is found a promising EOR method for certain heavy oil reservoirs. In this work, a simulation study ...

The two-part article aimed to investigate poloxamer 407-based microspheres as a novel platform for enhancing and controlling the delivery of atenolol across the oromucosal tissue. In the Part I of the work, atenolol-loaded poloxamers 407 microparticles were prepared by the solvent free spray congealing technology. This approach was feasible upon the high viscosity of the systems allowing for high loaded (20% w/w) non-aggregated microspheres. Several formulations were studied and the results demonstrated that the drug release patterns, solubility data, mucoadhesion to buccal tissue and gelling properties in saliva could be modified by adding different amount of an amphiphilic polymer-lipid excipient (Gelucire(®) 50/13) to poloxamer 407. Particularly, microspheres based only on poloxamer 407 exhibited very high solubility, mucoadhesive strength and gelling behaviour. To assess their potential as matrix for buccal application, the gelling property and the drug release from tablets obta...

We investigated the effects of corticosteroid and doxycycline on expression of matrix metalloproteinase (MMP)-9 and inflammatory cytokines and activation of mitogen-activated protein kinase (MAPK) signaling pathways, c-jun N-terminal kinases (JNK), extracellular-regulated kinases (ERK) and p38, in experimental murine dry eye. Experimental dry eye (EDE) was created in C57BL6 mice, with or without or topical treatment consisting of 1% methylprednisolone, 0.025% doxycycline or balanced salt solution four times per day. MMP-9 expression in the cornea epithelia was evaluated by laser scanning confocal microscopy. Gelatinase activity in the cornea was evaluated by in situ zymography and MMP-9 activity in tear washings was evaluated by gelatin zymography. Total and phosphorylated MAPKs (JNK1/2, ERK1/2, p38) were detected by Luminex immunobead assay. Levels of MMP-9, interleukin (IL)-1alpha, IL-1beta and tumor necrosis factor (TNF)-alpha RNA transcripts were evaluated by real-time PCR. MMP-9 immunoreactivity was localized to the apical corneal epithelial cell membranes in normal control eyes. Desiccating stress significantly increased production of MMP-9 by the corneal epithelium and increased its activity in the corneal epithelium and tear fluid. Dryness also increased expression of IL-1alpha, IL-1beta and TNF-alpha mRNA and stimulated phosphorylation of JNK1/2, ERK1/2 and p38 MAPKs in the corneal epithelium. Both methylprednisolone and doxycycline reduced expression and activity of MMP-9, decreased levels of inflammatory cytokines transcripts and reduced activation of MAPKs in the corneal epithelium in response to EDE. Desiccating stress stimulates expression of MMP-9, IL-1alpha, IL-1beta and TNF-alpha mRNA , as well as activates MAPK signaling pathways in the corneal epithelium. Both corticosteroid and doxycycline suppressed this molecular stress response.

The currently available experimental data supports the hypothesis that the neuroprotective effect of dimebon is related to the protection of the brain-mitochondria from neurodegeneration. In this study, the influence of dimebon on mitochondria was investigated to gain a better understanding of the neuroprotective effects of this drug. Here, we demonstrate that dimebon enhances the resistance of the isolated rat brain and liver mitochondria to the induction of mitochondrial permeability transition (MPT) by calcium ions even in the presence of atractyloside, a MPT pore (MPTP) opener, but is ineffective against atractyloside-induced mitochondria swelling. Unlike cyclosporine A (CsA), a MPTP inhibitor, Dimebon does not influence the adenine nucleotide translocase (ANT) conformational changes and is not able to prevent the MPT of de-energized mitochondria. Using three different assays, and using amyloid-β peptide for inducing mitochondrial toxicity, we show that the influence of dimebon ...

The permeability and strength of pervious concrete depend on the particle sizes and proportions of the constituent materials of which the concrete is made of. In this paper, structural property and permeability of pervious concrete made with different coarse aggregate sizes is presented. For the different aggregate/cement ratio used in this study, coarse aggregate size 9.375 mm has higher compressive strength values compared to those made from 18.75 mm aggregate size while 18.75 mm aggregate size had higher permeability value compared to that of 9.38 mm. The average specific gravity of the two aggregates sizes used was 2.7. Aggregate/cement ratio of 6:1, 8:1 and 10:1 respectively were used to produce three different batches of fresh concrete using 18.75mm aggregate size and same ratios were used for 9.375mm coarse aggregate size to produce another three different batches. In each case, aggregate/cement ratio of 6:1 gave the highest compressive strength compared to other aggregate/ce...

Cyclodextrins are widely used excipients in pharmaceutical formulations. They are mainly utilized as solubilizers and absorption enhancers, but recent results revealed their effects on cell membranes and pharmacological barriers. In addition to the growing knowledge on their interaction with plasma membranes, it was confirmed that cyclodextrins are able to enter cells by endocytosis. The number of the tested cyclodextrins was limited, and the role of this mechanism in drug absorption and delivery is not known. Our aim was to examine the endocytosis of fluorescently labeled hydroxypropyl-β-cyclodextrin, random methyl-β-cyclodextrin and soluble β-cyclodextrin polymer, and the cellular uptake of the fluorescent paclitaxel derivative-random methyl-β-cyclodextrin complex. The studied cyclodextrin derivatives were able to enter Caco-2 intestinal cells and localized in vesicles in the cytoplasm, while their permeability was very limited through Caco-2 monolayers. We demonstrated for the fi...

Alpha-tocopherol (AT) is the vitamin E homologue with the highest in vivo biological activity. AT protects against the carcinogenic and mutagenic activity of ionizing radiation and chemical agents, and possibly against UV-induced cutaneous damage. For stability consideration, alpha-tocopherol is usually used as its prodrug ester, alpha-tocopherol acetate (ATA), which once absorbed into the skin is hydrolyzed to alpha-tocopherol, the active form. The objective of this research was to characterize in vitro the permeation properties of ATA from various solutions and gel formulations. Permeation studies were conducted using modified Franz diffusion cells and human cadaver skin as the membrane. Specifically, 5% (w/w) alpha-tocopherol acetate was formulated in the following vehicles: ethanol, isopropyl myristate, light mineral oil, 1% Klucel gel in ethanol, and 3% Klucel gel in ethanol (w/w). The receiver temperature was 37 degrees C. Samples from the receiver were collected at 2, 4, 6, 8...