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At least 415 records · Page 23Linked to original sources
PubMed2005

Design principles of chemical penetration enhancers for transdermal drug delivery.

Chemical penetration enhancers (CPEs) are present in a large number of transdermal, dermatological, and cosmetic products to aid dermal absorption of curatives and aesthetics. This wide spectrum of use is based on only a handful of molecules, the majority of which belong to three to four typical chemical functionalities, sporadically introduced as CPEs in the last 50 years. Using >100 CPEs representing several chemical functionalities, we report on the fundamental mechanisms that determine the barrier disruption potential of CPEs and skin safety in their presence. Fourier transform infrared spectroscopy studies revealed that regardless of their chemical make-up, CPEs perturb the skin barrier via extraction or fluidization of lipid bilayers. Irritation response of CPEs, on the other hand, correlated with the denaturation of stratum corneum proteins, making it feasible to use protein conformation changes to map CPE safety in vitro. Most interestingly, the understanding of underlying molecular forces responsible for CPE safety and potency reveals inherent constraints that limit CPE performance. Reengineering this knowledge back into molecular structure, we designed >300 potential CPEs. These molecules were screened in silico and subsequently tested in vitro for molecular delivery. These molecules significantly broaden the repertoire of CPEs that can aid the design of optimized transdermal, dermatological, and cosmetic formulations in the future.

Administration, Cutaneous↗
PubMed1999

Phytoremediation of methylmercury pollution: merB expression in Arabidopsis thaliana confers resistance to organomercurials.

Methylmercury is an environmental toxicant that biomagnifies and causes severe neurological degeneration in animals. It is produced by bacteria in soils and sediments that have been contaminated with mercury. To explore the potential of plants to extract and detoxify this chemical, we engineered a model plant, Arabidopsis thaliana, to express a modified bacterial gene, merBpe, encoding organomercurial lyase (MerB) under control of a plant promoter. MerB catalyzes the protonolysis of the carbon---mercury bond, removing the organic ligand and releasing Hg(II), a less mobile mercury species. Transgenic plants expressing merBpe grew vigorously on a wide range of concentrations of monomethylmercuric chloride and phenylmercuric acetate. Plants lacking the merBpe gene were severely inhibited or died at the same organomercurial concentrations. Six independently isolated transgenic lines produced merBpe mRNA and MerB protein at levels that varied over a 10- to 15-fold range, and even the lowest levels of merBpe expression conferred resistance to organomercurials. Our work suggests that native macrophytes (e.g., trees, shrubs, grasses) engineered to express merBpe may be used to degrade methylmercury at polluted sites and sequester Hg(II) for later removal.

Air Pollutants↗
PubMed2003

Structure-property relationships of silicone biofouling-release coatings: effect of silicone network architecture on pseudobarnacle attachment strengths.

Model silicone foul-release coatings with controlled molecular architecture were evaluated to determine the effect of compositional variables such as filler loading and crosslink density on pseudobarnacle attachment strength. Pseudobarnacle adhesion values correlated with filler loadings in both condensation and hydrosilylation-cured silicones. Variation of crosslink density of hydrosilylation-cured silicones had an insignificant effect on attachment strength. X-ray photoelectron spectroscopy (XPS) indicated that the mode of failure upon detachment of the pseudobarnacle was dependent upon the crosslink density; samples with high crosslink density failed cohesively within the silicone.

Adhesiveness↗
PubMed2002

Pediocin PA-1, a wide-spectrum bacteriocin from lactic acid bacteria.

Pediocin PA-1 is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industries. This antimicrobial peptide is the most extensively studied class Ila (or pediocin family) bacteriocin, and it has been sufficiently well characterized to be used as a food biopreservative. This review focuses on the progress that have been made in the elucidation of its structure, mode of action, and biosynthesis, and includes an overview of its applications in food systems. The aspects that need further research are also addressed. In the future, protein engineering, genetic engineering and/or chemical synthesis may lead to the development of new antimicrobial peptides with improved properties, based on some features of the pediocin PA-1 molecule.

Amino Acid Sequence↗
PubMed2001

Purification of non-toxic, biodegradable arginine-based gemini surfactants, bis(Args), by ion exchange chromatography.

This paper presents an environmentally improved procedure for the preparative purification of a series of arginine-based gemini surfactants. The technique used was cation-exchange chromatography. Mixtures of boric-borate buffer, co-solvent (ethanol), and sodium chloride were tested as eluents. The influence of the buffer pH and the amount of co-solvent on the chromatographic process was studied for the model compound bis(Nalpha-lauroyl-L-arginine) 1,3-propanediamide dihydrochloride, C3(LA)2, and purification conditions were established. The method was scaled-up to the multigram level for C3(LA)2 and the rest of the series. The proposed preparative procedure involves simple equipment, low cost materials, and minimal amounts of solvent (water/ethanol), with low toxicity.

Arginine↗
PubMed2006

The role of molecular modeling in bionanotechnology.

Molecular modeling is advocated here as a key methodology for research and development in bionanotechnology. Molecular modeling provides nanoscale images at atomic and even electronic resolution, predicts the nanoscale interaction of unfamiliar combinations of biological and inorganic materials, and evaluates strategies for redesigning biopolymers for nanotechnological uses. The methodology is illustrated in this paper through reviewing three case studies. The first one involves the use of single-walled carbon nanotubes as biomedical sensors where a computationally efficient, yet accurate, description of the influence of biomolecules on nanotube electronic properties through nanotube-biomolecule interactions was developed; this development furnishes the ability to test nanotube electronic properties in realistic biological environments. The second case study involves the use of nanopores manufactured into electronic nanodevices based on silicon compounds for single molecule electrical recording, in particular, for DNA sequencing. Here, modeling combining classical molecular dynamics, material science and device physics, described the interaction of biopolymers, e.g., DNA, with silicon nitrate and silicon oxide pores, furnished accurate dynamic images of pore translocation processes, and predicted signals. The third case study involves the development of nanoscale lipid bilayers for the study of embedded membrane proteins and cholesterol. Molecular modeling tested scaffold proteins, redesigned apolipoproteins found in mammalian plasma that hold the discoidal membranes in the proper shape, and predicted the assembly as well as final structure of the nanodiscs. In entirely new technological areas such as bionanotechnology, qualitative concepts, pictures and suggestions are sorely needed; these three case studies document that molecular modeling can serve a critical role in this respect, even though it may still fall short on quantitative precision.

Biosensing Techniques↗
PubMed1999

Efficient site specific removal of a C-terminal FLAG fusion from a Fab' using copper(II) ion catalysed protein cleavage.

The peptide sequence (N)DKTH(C) was investigated as a site for efficient, specific cleavage of a fusion protein by cupric ions using a humanised gamma1 Fab' as a model protein. The native upper hinge (N)DKTH(C) sequence was mutated to create a site resistant to cleavage by cupric ions and a (N)DKTH(C) sequence introduced between the hinge and a C-terminal FLAG peptide. Incubation of Fab' with Cu2+ at 62 degrees C at alkaline pHs resulted in removal of the FLAG peptide with efficiencies of up to 86%. Cleavage conditions did not detrimentally affect the Fab' protein. Use of the (N)DKTH(C) sequence along with cupric ions may provide a cost-effective method for large scale proteolytic cleavage of fusion proteins.

Amino Acids↗
PubMed1994

Biological assessment of aquatic pollution: a review, with emphasis on plants as biomonitors.

In a number of disciplines including ecology, ecotoxicology, water quality management, water resource management, fishery biology etc., there is significant interest in the testing of new materials, environmental samples (of water or sediments) and specific sites, in terms of their effects on biota. In the first instance, we consider various sources of aquatic pollution, sources typically associated with developed areas of the world. Historically, much water quality assessment has been performed by researchers with a background in chemistry or engineering, thus chemical analysis was a dominant form of assessment. However, chemical analyses, particularly of such materials as organochlorines and polyaromatic hydrocarbons can be expensive, and local environmental factors may cause the actual exposure of an organism to be little correlated with chemical concentrations in the surrounding water or sediments. To a large extent toxicity testing has proceeded independently of environmental quality assessment in situ, and the work has been done by different, and differently-trained researchers. Here we attempt to bring together the various forms of biological assessment of aquatic pollution, because in our opinion it is worth developing a coherent framework for the application of this powerful tool. Biotic assessment in its most primitive form involves the simple tracking of mortality in exposed organisms. However, in most natural environments it is extended, chronic exposure to contaminants that has the most wide-ranging and irreversible repercussions--thus measures of sub-lethal impairment are favoured. From an ecological standpoint, it is most valuable to assess ecological effects by direct study of in situ contaminant body burdens and impairment of growth and reproduction compared with 'clean' sites. A distinction is made here between bioindication and biomonitoring, and a case is made for including aquatic macrophytes (angiosperms) in studies of contaminant levels and effects in the biota. It is apparent that there is a concurrent need for laboratory-based testing of new industrial by-products before any are released in the environment, and such studies should aid the investigation of mechanisms and modes of toxicity, but environmental assessment, and tracking of improvements in environmental quality are most effectively achieved by active biomonitoring experiments.

Ecology↗