Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

In recent years there has been considerable effort to understand the interaction of nanomaterials with the skin. In this study we use an in vivo mouse model of allergic contact dermatitis to investigate how nanoparticles (NPs) may alter allergic responses in skin. We investigate a variety of NPs that vary in size, charge and composition. Results show that small (<200 nm) negative and neutral charged NPs exhibit an immunosuppressive effect but that positively charged NPs do not. Confocal imaging suggests positively charged NPs may penetrate skin to a lesser extent and thereby are less able interact with and alter the local immune responses. Interestingly, negatively charged silica (20 nm) NPs suppress allergic response to two chemically distinct sensitizers; 1-fluoro-2, 4-dinitrobenzene and 2-deoxyurushiol. Skin wiping and NP application time studies suggest that the immunomodulatory mechanism is not due solely to the blocking of sensitizer adduct formation in skin. Results suggest that NPs modulate early immune events that impact mast cell degranulation. Our study shows for the first time the potential to modulate the elicitation phase of the allergic response which depends on the NP charge and composition. These finding can be used to inform the design topical therapeutics to mitigate allergic responses in skin.

/ In this article, we suggest that a landscape approach might be useful in evaluating the effects of cumulative impacts on freshwater wetlands. The reason for using this approach is that most watersheds contain more than one wetland, and effects on water quality depend on the types of wetlands and their position in the landscape. Riparian areas that border uplands appear to be important sites for nitrogen processing and retention of large sediment particles. Fine particles associated with high concentrations of phosphorus are retained in downstream wetlands, where flow rates are slowed and where the surface water passes through plant litter. Riverine systems also may play an important role in processing nutrients, primarily during flooding events. Lacustrine wetlands appear to have the least impact on water quality, due to the small ratio of vegetated surface to open water. Examples are given of changes that occurred when the hydrology of a Maryland floodplain was altered.There is little doubt that freshwater wetlands can significantly improve water quality and, with few exceptions, most have been shown to perform that function (Kelly and Harwell 1985, Nixon andLee 1988). However, numerous questions about the relationship between wetlands and water quality are still unanswered because many types of freshwater wetlands have not been adequately studied (LaBaugh 1986, Nixon andLee 1988). Most water quality research projects have been short term and have not included input-output analyses (Whigham and Bayley 1979, Howard-Williams 1985, Nixon and Lee 1988, especially for hydrologic variables (Carter 1986, LaBaugh 1986).The need for long-term studies and detailed input-output analyses has been recognized over and over again in recent reviews of the freshwater wetland literature (Kadlec and Kadlec 1979, Whigham and Bayley 1979, Zedler and Kentula 1985, LaBaugh 1986, Nixon and Lee 1979, Richardson 1988, and has been documented in recommendations to the National Science Foundation (NSF) and many other federal agencies (Larson and Loucks 1978, Clark andClark 1979). To date the Long-Term Ecological Research Program (LTER), funded by NSF, is the only national program devoted to long-term ecological research, and wetland ecosystem research is the main focus of only two sites. Unfortunately, institutional support of long-term wetlands research has not moved very far from the initial pronouncements made in the late KEY WORDS: Cumulative impacts; Freshwater wetlands; Lacustrine; Landscape ecology; Palustrine; Riparian; Riverine; Sediment; Water quality; Wetland continuum1970s. There are many reasons for this, and our purpose is not to make yet another call for those types of projects; the need is still obvious. In this article, we hope to provide a framework that might be used to evaluate how cumulative impacts to wetlands might affect or alter water quality. We also hope that this framework may lead to suggestions about the types of research that should be conducted. The approach that we use is an extension of the ...

Debate about the biological effects of biodiesel exhaust emissions exists due to variation in methods of exhaust generation and biological models used to assess responses. Because studies in cells do not necessarily reflect the integrated response of a whole animal, experiments were conducted in two human cell lines representing bronchial epithelial cells and macrophages and female mice using identical particle suspensions of raw exhaust generated by a Volkswagen light-duty diesel engine using petrodiesel (B0) and a biodiesel blend (B20: 20% soy biodiesel/80% B0 by volume). Tailpipe particle emissions measurement showed B0 generated two times more particle mass, larger ultrafine particle number distribution modes, and particles of more nonpolar organic composition than the B20 fuel. Biological assays (inflammatory mediators, oxidative stress biomarkers) demonstrated that particulate matter (PM) generated by combustion of the two fuels induced different responses in in vitro and in vivo models. Concentrations of inflammatory mediators (Interleukin-6, IL-6; Interferon-gamma-induced Protein 10, IP-10; Granulocyte-stimulating factor, G-CSF) in the medium of B20-treated cells and in bronchoalveolar lavage fluid of mice exposed to B20 were ~20–30% higher than control or B0 PM, suggesting that addition of biodiesel to diesel fuels will reduce PM emissions but not necessarily adverse health outcomes.

BackgroundThe effects of carbon nanotubes on skin toxicity have not been extensively studied; however, our lab has previously shown that a carboxylated multi-walled carbon nanotube (MWCNT) exacerbates the 2, 4-dinitrofluorobenzene induced contact hypersensitivity response in mice. Here we examine the role of carboxylation in MWCNT skin toxicity.ResultsMWCNTs were analyzed by transmission electron microscopy, zetasizer, and x-ray photoelectron spectroscopy to fully characterize the physical properties. Two MWCNTs with different levels of surface carboxylation were chosen for further testing. The MWCNTs with a high level of carboxylation displayed increased cytotoxicity in a HaCaT keratinocyte cell line, compared to the MWCNTs with intermediate levels of carboxylation. However, neither functionalized MWCNT increased the level of in vitro reactive oxygen species suggesting an alternative mechanism of cytotoxicity. Each MWCNT was tested in the contact hypersensitivity model, and only the MWCNTs with greater than 20% surface carboxylation exacerbated the ear swelling responses. Analysis of the skin after MWCNT exposure reveals that the same MWCNTs with a high level of carboxylation increase epidermal thickness, mast cell and basophil degranulation, and lead to increases in polymorphonuclear cell recruitment when co-administered with 2, 4-dinitrofluorobenzene.ConclusionsThe data presented here suggest that acute, topical application of low doses of MWCNTs can induce keratinocyte cytotoxicity and exacerbation of allergic skin conditions in a carboxylation dependent manner.Electronic supplementary materialThe online version of this article (10.1186/s12989-018-0285-x) contains supplementary material, which is available to authorized users.

Lamb losses to predation have historically ranged from 4% to 8% in the western United States but most data are over 30 yr old. We repeated a sheep depredation study conducted from 1972 through 1975 on Cedar Mountain, Utah, to determine how predation rates have changed in the last three decades. Pastures and herd sizes were similar (1 730 lambs) between our study (2006 and 2007) and the prior one. Additionally, 40% of the ranchers in our study also participated in the prior study. During 2006 and 2007, 5.8% of all lambs on Cedar Mountain were lost to all causes compared to 9.5% during the 1970s. Predators were responsible for 87% of all verified lamb losses during our study versus 83% during the 1970s. We estimated that 4.9% of all lambs on Cedar Mountain were killed by predators during our study compared to 7.9% during the 1970s. During our study, coyotes (Canis latrans Say) were responsible for 67% of the depredated lambs, cougars (Felis concolor Linnaeus) for 31%, and black bears (Ursus americanus Pallas) for 2%. During the 1970s, coyotes killed 98% of all depredated lambs, cougars killed 2%, and bears killed 0%. In addition to the increase in cougar kills, the other change on Cedar Mountain since the 1970s is that California condors (Gymnogyps californianus Shaw) have begun scavenging lamb carcasses. Our results indicate that increasing populations of cougars, black bears, and condors have complicated the task of protecting lambs from predators. Resumen Las pérdidas de corderos debido a la depredación han oscilado históricamente entre 4 a 8% en el oeste de Estados Unidos pero la mayoría de estos datos tienen más de 30 añ os. Repetimos un estudio de depredación con ovejas que se condujo entre 1972 y 1975 en Cedar Mountain, en Utah para determinar cómo han cambiado las tasas de depredación en las últimas tres décadas. El tamañ o de los potreros y los hatos fueron similares (1 730 corderos) entre nuestro estudio (2006 y 2007) y el estudio anterior. Además, el 40% de los ganaderos en nuestro estudio también participaron en el estudio anterior. Durante 2006 y 2007, la pe´rdida total de corderos de Cedar Mountain fue 5.8%, debido a diferentes causas en comparación de 9.5% durante la década de 1970. Los depredadores fueron responsables del 87% de todas las pe´rdidas verificadas en nuestro estudio contra 83% de las pe´rdidas durante 1970. Se estimó que el 4.9% de todos los corderos de Cedar Mountain fueron matados por predadores durante nuestro estudio, comparado con 7.9% durante 1970. En nuestro estudio, los coyotes (Canis latrans Say) fueron responsables del 67% de los corderos depredados, mientras que los pumas (Felis concolor Linnaeus) 31%, y los osos negros (Ursus americanus Pallas) el 2%. Durante la de´cada de 1970, los coyotes mataron a 98% de todos los corderos depredados, pumas un 2%, y los osos a 0%. Además del aumento en las muertes por los pumas, el otro cambio en Cedar Mountain desde la de´cada de 1970 es que los cóndores (Gymnogyps californianus Shaw) de California han comenzado a consumir los cadáveres ...

Amorphous silicon dioxide nanoparticles (SiNPs) are ubiquitous, and they are currently found in cosmetics, drugs, and foods. Biomedical research is also focused on using these nanoparticles as drug delivery and bio-sensing platforms. Due to the high potential for skin exposure to SiNPs, research into the effect of topical exposure on both healthy and inflammatory skin models is warranted. While we observe only minimal effects of SiNPs on healthy mouse skin, there is an immunomodulatory effect of these NPs in a model of allergic contact dermatitis. The effect appears to be mediated partly by keratinocytes and results in decreases in epidermal hyperplasia, inflammatory cytokine release, immune cell infiltration, and a subsequent reduction in skin swelling. Additional research is required to further our mechanistic understanding and to validate the extent of this immunomodulatory effect in human subjects in order to assess the potential prophylactic use of SiNPs for treating allergic skin conditions.

Diesel engine emissions are an important source of ultrafine particulate matter (PM) in both ambient air and many occupational settings. Biodiesel is a popular, ‘green’ alternative to petroleum diesel fuel, but little is known about the impact of ‘real world’ biodiesel combustion on workplace PM concentrations and particle characteristics including size, morphology, and composition; or on biological responses. The objectives of the present work were to characterize PM workplace concentrations and tailpipe emissions produced by the combustion of commercially purchased low sulfur petrodiesel and a waste grease B20 blend (20% biodiesel/80% petrodiesel by volume) in heavy duty diesel (HDD) nonroad equipment operating in a ‘real world’ rural recycling center. Furthermore, we assessed the in vitro responses of cell lines representing human lung epithelial cells (BEAS-2B) and macrophages (THP-1) after 24 h of exposure to these real-world particles. Compared to petroleum diesel, use of B20 in HDD equipment resulted in lower mass concentrations of PM2.5, PM<0.25 (particle diameter less than 2.5 and 0.25 micrometer, respectively), and elemental carbon. Transmission electron analysis of PM showed that primary particle size and morphology were similar between fuel types. Metals composition analysis revealed differences between fuels, with higher Fe, Al, V, and Se measured during B20 use, and higher As, Cd, Cu, Mn, Ni and Pb concentrations measured during petrodiesel use. In vitro responses varied between fuels but data supported that waste grease B20 particles elicited inflammatory responses in human macrophages and lung epithelial cells comparable to petrodiesel particles. However, the effects were more pronounced with B20 than petrodiesel at the same mass concentration. Since the primary particle size and morphology were similar between fuels, it is likely that the differential results seen in the in vitro assays points to differences in the composition of the PM. Future research should focus on the organic carbon and metals speciation and potential impact of real world particles on reactive oxygen species generation and mechanisms for differences in the cellular inflammatory responses.