3,468 research outputs found
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Mechanisms of burst release from pH-responsive polymeric microparticles.
Microencapsulation of drugs into preformed polymers is commonly achieved through solvent evaporation techniques or spray drying. We compared these encapsulation methods in terms of controlled drug release properties of the prepared microparticles and investigated the underlying mechanisms responsible for the “burst release” effect. Using two different pH-responsive polymers with a dissolution threshold of pH 6 (Eudragit L100 and AQOAT AS-MG), hydrocortisone, a model hydrophobic drug, was incorporated into microparticles below and above its solubility within the polymer matrix. Although, spray drying is an attractive approach due to rapid particle production and relatively low solvent waste, the oil-in-oil microencapsulation method is superior in terms of controlled drug release properties from the microparticles. Slow solvent evaporation during the oil-in-oil emulsification process allows adequate time for drug and polymer redistribution in the microparticles and reduces uncontrolled drug burst release. Electron microscopy showed that this slower manufacturing procedure generated non-porous particles whereas thermal analysis and X-ray diffractometry showed that drug loading above the solubility limit of the drug in the polymer generated excess crystalline drug on the surface of the particles. Raman spectral mapping illustrated that drug was homogeneously distributed as a solid solution in the particles when loaded below saturation in the polymer with consequently minimal burst release
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Thermodynamic and kinetic properties of interpolymer complexes assessed by isothermal titration calorimetry and surface plasmon resonance
Interpolymer complexes (IPCs) formed between complimentary polymers in solution have shown a wide range of applications from drug delivery to biosensors. This work describes the combined use of isothermal titration calorimetry and surface plasmon resonance to investigate the thermodynamic and kinetic processes during hydrogen-bonded interpolymer complexation. Varied polymers that are commonly used in layer-by-layer coatings and pharmaceutical preparations were selected to span a range of chemical functionalities including some known IPCs previously characterized by other techniques, and other polymer combinations with unknown outcomes. This work is the first to comprehensively detail the thermodynamic and kinetic data of hydrogen bonded IPCs, aiding understanding and detailed characterization of the complexes. The applicability of the two techniques in determining thermodynamic, gravimetric and kinetic properties of IPCs is considered
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Bioaccessibility of PBDEs present in indoor dust: a novel dialysis membrane method with a Tenax TA® absorption sink
Human uptake of flame retardants (FRs) such as polybrominated diphenyl ethers (PBDEs) via indoor dust ingestion is commonly considered as 100% bioaccessible, leading to potential risk overestimation. Here, we present a novel in vitro colon-extended physiologically-based extraction test (CE-PBET) with Tenax TA® as an absorptive "sink" capable to enhance PBDE gut bioaccessibility. A cellulose-based dialysis membrane (MW cut-off 3.5kDa) with high pH and temperature tolerance was used to encapsulate Tenax TA®, facilitating efficient physical separation between the absorbent and the dust, while minimizing re-absorption of the ingested PBDEs to the dust particles. As a proof of concept, PBDE-spiked indoor dust samples (n=3) were tested under four different conditions; without any Tenax TA® addition (control) and with three different Tenax TA® loadings (i.e. 0.25, 0.5 or 0.75g). Our results show that in order to maintain a constant sorptive gradient for the low MW PBDEs, 0.5g of Tenax TA® are required in CE-PBET. Tenax TA® inclusion (0.5g) resulted in 40% gut bioaccessibility for BDE153 and BDE183, whereas greater bioaccessibility values were seen for less hydrophobic PBDEs such as BDE28 and BDE47 (~60%). When tested using SRM 2585 (n=3), our new Tenax TA® method did not present any statistically significant effect (p>0.05) between non-spiked and PBDE-spiked SRM 2585 treatments. Our study describes an efficient method where due to the sophisticated design, Tenax TA® recovery and subsequent bioaccessibility determination can be simply and reliably achieved
Analysis of the 2007/8 Defra Farm Business Survey Energy Module
Key points This study has delivered an invaluable baseline estimate of energy
use and greenhouse gas (GHG) emissions on commercial farms in England. Energy
use and GHG emissions associated with particular commodities were quantified and
results broadly agreed with those derived by Life Cycle Assessment, but with
much scatter in the environmental performance of farms.Direct energy use on
farms was generally less that indirect (embedded) energy use, except for
horticulture, which is dominated by heating fuel use. In contrast, most GHG
emissions are incurred on farms, rather than as embedded emissions.Scatter in
both environmental and economic performance underlies the somewhat disappointing
finding of no clear positive link between farm financial performance and energy
use or GHG emissions. However, the mere existence of these ranges shows that
there is scope for improvement in both financial and environmental performance
and that there is no apparent barrier for both to be achievable in harmony. The
recording of such farm-level energy data is essential for the future, as it
should enable improvements to be made in efficiency of energy use. The improved
UK agricultural GHG inventory will depend on high quality energy data on
agricultural activities. This study will be invaluable in identifying the level
of detail needed. Future data requirements include: contractor work rates and
fuel use per unit area and per unit time, fertiliser and pesticide use by brand
name, enhanced output data, especially animal live weights, and horticultural
produce recorded by weight rather than by value
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CDASH: a cloud-enabled program for structure solution from powder diffraction data
The simulated annealing approach to crystal structure determination from powder diffraction data, as implemented in the DASH program, is readily amenable to parallelization at the individual run level. Very large scale increases in speed of execution can be achieved by distributing individual DASH runs over a network of computers. The CDASH program delivers this by using
scalable on-demand computing clusters built on the Amazon Elastic Compute Cloud service. By way of example, a 360 vCPU cluster returned the crystal structure of racemic ornidazole (Z0 = 3, 30 degrees of freedom) ca 40 times faster than a typical modern quad-core desktop CPU. Whilst used here specifically for DASH, this approach is of general applicability to other packages that are
amenable to coarse-grained parallelism strategies
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Adhesion of thiolated silica nanoparticles to urinary bladder mucosa: effects of PEGylation, thiol content and particle size
Intravesical drug administration is used to deliver cytotoxic agents through a catheter to treat bladder cancer. One major limitation of this approach is poor retention of the drug in the bladder due to periodic urine voiding. Mucoadhesive dosage forms thus offer significant potential to improve drug retention in the bladder. Here, we investigate thiolated silica nanoparticles retention on porcine bladder mucosa in vitro, quantified through Wash Out50 (WO50) values, defined as the volume of liquid necessary to remove 50% of the adhered particles from a mucosal tissue. Following irrigation with artificial urine solution, the thiolated nanoparticles demonstrate significantly greater retention (WO50 up to 36 mL) compared to non-mucoadhesive dextran (WO50 7 mL), but have weaker mucoadhesive properties than chitosan (WO50 89 mL). PEGylation of thiolated silica reduces their mucoadhesion with WO50 values of 29 and 8 mL for particles decorated with 750 and 5000 Da PEG, respectively. The retention of thiolated silica nanoparticles is dependent on their thiol group contents and physical dimensions
Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra
Compartmentalized redox faults are common to ageing diseases. Dietary constituents are catabolized to NAD(H) donating electrons producing proton-based bioenergy in coevolved, cross-species and cross-organ networks. Nicotinamide and NAD deficiency from poor diet or high expenditure causes pellagra, an ageing and dementing disorder with lost robustness to infection and stress. Nicotinamide and stress induce Nicotinamide-N-methyltransferase (NNMT) improving choline retention but consume methyl groups. High NNMT activity is linked to Parkinson's, cancers, and diseases of affluence. Optimising nicotinamide and choline/methyl group availability is important for brain development and increased during our evolution raising metabolic and methylome ceilings through dietary/metabolic symbiotic means but strict energy constraints remain and life-history tradeoffs are the rule. An optimal energy, NAD and methyl group supply, avoiding hypo and hyper-vitaminoses nicotinamide and choline, is important to healthy ageing and avoids utilising double-edged symbionts or uncontrolled autophagy or reversions to fermentation reactions in inflammatory and cancerous tissue that all redistribute NAD(P)(H), but incur high allostatic costs
Forest landscape restoration in the drylands of Latin America
Forest Landscape Restoration (FLR) involves the ecological restoration of degraded forest landscapes, with the aim of benefiting both biodiversity and human well-being. We first identify four fundamental principles of FLR, based on previous definitions. We then critically evaluate the application of these principles in practice, based on the experience gained during an international, collaborative research project conducted in six dry forest landscapes of Latin America. Research highlighted the potential for FLR; tree species of high socioeconomic value were identified in all study areas, and strong dependence of local communities on forest resources was widely encountered, particularly for fuelwood. We demonstrated that FLR can be achieved through both passive and active restoration approaches, and can be cost-effective if the increased provision of ecosystem services is taken into account. These results therefore highlight the potential for FLR, and the positive contribution that it could make to sustainable development. However, we also encountered a number of challenges to FLR implementation, including the difficulty of achieving strong engagement in FLR activities among local stakeholders, lack of capacity for community-led initiatives, and the lack of an appropriate institutional and regulatory environment to support restoration activities. Successful implementation of FLR will require new collaborative alliances among stakeholders, empowerment and capacity building of local communities to enable them to fully engage with restoration activities, and an enabling public policy context to enable local people to be active participants in the decision making process. © 2012 by the author(s). Published here under license by the Resilience Alliance
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Using pH abnormalities in diseased skin to trigger and target topical therapy
Abstract
Purpose: The pH discrepancy between healthy and atopic dermatitis skin was identified as a site specific trigger for delivering hydrocortisone from microcapsules.
Methods: Using Eudragit L100, a pH-responsive polymer which dissolves at pH 6, hydrocortisone-loaded microparticles were produced by oil-in-oil microencapsulation or spray drying. Release and permeation of hydrocortisone from microparticles alone or in gels was assessed and preliminary stability data was determined.
Results: Drug release from microparticles was pH-dependent though the particles produced by spray drying also gave significant non-pH dependent burst release, resulting from their porous nature or from drug enrichment on the surface of these particles. This pH-responsive release was maintained upon incorporation of the oil-in-oil microparticles into Carbopol- and HPMC-based gel formulations. In-vitro studies showed 4 to 5-fold higher drug permeation through porcine skin from the gels at pH 7 compared to pH 5.
Conclusions: Permeation studies showed that the oil-in-oil generated particles deliver essentially no drug at normal (intact) skin pH (5.0 – 5.5) but that delivery can be triggered and targeted to atopic dermatitis skin where the pH is elevated. The incorporation of these microparticles into Carbopol- and HPMC-based aqueous gel formulations demonstrated good stability and pH-responsive permeation into porcine skin
Geodesic Deviation in Regge Calculus
Geodesic deviation is the most basic manifestation of the influence of
gravitational fields on matter. We investigate geodesic deviation within the
framework of Regge calculus, and compare the results with the continuous
formulation of general relativity on two different levels. We show that the
continuum and simplicial descriptions coincide when the cumulative effect of
the Regge contributions over an infinitesimal element of area is considered.
This comparison provides a quantitative relation between the curvature of the
continuous description and the deficit angles of Regge calculus. The results
presented might also be of help in developing generic ways of including matter
terms in the Regge equations.Comment: 9 pages. Latex 2e with 5 EPS figures. Submitted to CQ
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