Biomedical subjects

Andrew M Howe

Publications and source records attributed to Andrew M Howe.

11 recordsLinked to original sources

PubMed2007

Steric interactions between physically adsorbed polymer-coated colloidal particles: soft or hard?

The steric interaction potential between colloidal particles imparted by adsorbed polymer layers is directly related to their structure. Due to the complexity of these interfacial structures, the steric potential may behave differently at different interparticle separations. In this study, we proposed a combined model of the equivalent hard-sphere model (EHS) and the Hayter-Penfold/Yukawa model (HPY) to describe the steric potential due to adsorbed homopolymers on colloidal particles. The EHS potential describes the dense train/small-loop region and the HPY potential the more diffuse tail/long-loop region. The steric potential was extracted from the structure factors measured by small-angle neutron scattering (SANS). It was found that this combined model gave better agreement with experimental data than either of its component models alone. This study also shows that the adsorbed polymer layer in a good solvent partially collapses when the layers approach one another, which is also supported by an NMR solvent relaxation study.

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PubMed2006

Small-angle neutron scattering study of concentrated colloidal dispersions: the electrostatic/steric composite interactions between colloidal particles.

Small-angle neutron scattering was used to investigate the interactions in concentrated colloidal dispersions containing silica or polystyrene latex with adsorbed polyethyleneoxide (PEO). In these dispersions of charged particles, both electrostatic and steric repulsions are present. The PEO layer was made invisible to neutrons through contrast matching. The effect of the interparticle repulsion was clearly shown in the scattering spectra by the appearance of a peak at low Q. The effective potentials can be well described by the Hayter-Penfold/Yukawa (HPY) potential. In the silica dispersions studied, the layer thickness is small, hence the electrostatic potential dominates and the potential has a lower concentration dependence. In the dispersions of polystyrene latex, the adsorbed layer is thicker; consequently, the electrostatic potential dominates at low volume fraction (the potential has a lower concentration dependence), and the steric potential dominates at higher volume fraction (the potential has a higher concentration dependence). This study also suggests that when more than one potential is present the stronger one has a dominant influence in determining the structure factor. This finding makes it possible to describe the multicomponential interactions by a single function.

Journal Article↗

PubMed2006

Controlled association in suspensions of charged nanoparticles with a weak polyelectrolyte.

The properties of high-pH suspensions of mixtures of silica with low-molecular-weight samples of the water-soluble polymer polyethylenimine (PEI) have been studied. At pH > 10 and low ionic strength, silica nanoparticles are stabilized by a negative surface charge, and PEI has only a very low positive charge. The adsorption of PEI induces a localized positive charge on the segments of polymer closest to the silica surface. The parts of the molecule furthest away from the surface have little charge because of the high pH of the medium. The polymer-covered particle remains negatively charged, imparting some electrostatic stabilization. Suspensions of silica and low-molecular-weight PEI are low-viscosity fluids immediately after mixing, but aggregation occurs leading to the eventual gelation (or sedimentation at lower concentrations) of these mixtures, indicating colloidal instability. The gelation time passes through a minimum with increasing surface coverage. The rate of gelation increases exponentially with molecular weight: for molecular weight > or = 10,000 Da PEI, the instability is so severe that uniform suspensions cannot be produced using simple mixing techniques. The gelation rates increase rapidly with temperature, ionic strength, and reduction in pH. The rate of gelation increases with increasing particle concentration at low surface coverage but decreases at high coverage as a consequence of a small increase in pH. Gels are broken by application of high shear into aggregates that re-gel more rapidly than the original discrete coated particles.

Journal Article↗

PubMed2006

Controlled, simultaneous assembly of polyethylenimine onto nanoparticle silica colloids.

A novel precision-assembly methodology is described on the basis of the controlled, simultaneous assembly (CSA) of a core nanoparticle substrate and polyelectrolyte solutions. The method is capable of assembly rates at least as fast as 10(16) core particles s(-1) L(-1) and affords concentrated suspensions of stable colloids with an adsorbed polyelectrolyte. The resulting dispersions are highly homogeneous, have a low viscosity and narrow particle-size distribution, and are stable colloids, even at solid concentrations of at least 33 wt %. The adsorption isotherm and the saturation adsorption for polyethylenimine (PEI) assemblies onto a 15 nm silica colloid have been evaluated with 1H NMR spectroscopy. The saturation adsorption is highly dependent upon the pH at assembly and is given by the equation PEIa (micromol m(-2)) = 1.73pH - 1.89, R2 = 0.986, where micromoles refers to the concentration of the EI monomer. The saturation concentration increases from 6.8 micromol m(-2) at pH 5.0 to 13.7 micromol m(-2) at pH 9.0. The adsorbed polyelectrolyte may be cross-linked and thereby permanently fixed to the colloid surface to prepare nanoparticle-polyelectrolyte colloidal assemblies having enhanced colloid stability, high homogeneity, and a high fraction (>80%) of permanently adsorbed polyelectrolyte. These assemblies are stable at physiological pH and ionic strength and may represent ideal substrates for bioconjugation and, ultimately, the design of nanocarriers for in vivo applications.

Journal Article↗

PubMed2006

A small-angle X-ray scattering study of the interactions in concentrated silica colloidal dispersions.

The structure factors of colloidal silica dispersions at rather high volume fractions (from 0.055 to 0.22) were measured by small-angle X-ray scattering and fitted with both the equivalent hard-sphere potential model (EHS) and the Hayter-Penfold/Yukawa potential model (HPY). Both of these models described the interactions in these dispersions successfully, and the results were in reasonable agreement. The strength and range of the interaction potentials decreased with increasing particle volume fractions, which suggests shrinkage of the electrical double layer arising from an increase in the counterion concentration in the bulk solution. However, the interactions at the average interparticle separation increased as the volume fraction increased. The interaction ranges (delta) determined by the two models were very similar. Structure factors were also used to determine the size and volume fraction of the particles. The values of the size obtained from the structure factors were slightly larger than those obtained from the form factors; this difference is ascribed to the nonspherical shape and polydispersity of the colloidal particles. The volume fractions measured by these two methods were very similar and are both in good agreement with the independently measured results.

Journal Article↗

PubMed2006

The relationship between cleft lip, maxillary hypoplasia, hypoxia and phenytoin.

Cleft lip (CL) is a common malformation that has both genetic and exogenous causes. The main pharmaceutical cause is exposure to phenytoin during early facial development in the 5th to 6th weeks of gestation. Phenytoin also causes CL if administered to pregnant rats during the period of early facial development. Evidence is presented that in the pregnant rat, a teratogenic dose of phenytoin slows the early embryonic heart and causes a prolonged period of embryonic hypoxia. It is proposed that this hypoxia, through an undefined downstream mechanism, leads to the development of CL. The involvement of hypoxia in the pathogenesis of CL is in agreement with studies in mouse strains with a spontaneous rate of CL in which exposure to hypoxia has been shown to increase the rate and hyperoxia to decrease the rate. Other exogenous risk factors during pregnancy for human CL include maternal cigarette smoking, residence at high altitude and exposure to corticosteroids. It is suggested that these exposures all involve an increased risk of embryonic hypoxia. It has been proposed that phenytoin affects the embryonic heart by inhibition of the human-ether-a-go-go (HERG) potassium channel. Phenytoin also inhibits sodium and calcium channels and these properties may also be involved in the observed effect on the embryonic heart. Phenytoin-induced bradycardia leading to embryonic hypoxia may be an important mechanism by which phenytoin causes birth defects.

Animals↗

PubMed2005

Controlling porosity within colloidal heteroaggregates.

Heteroaggregates of cationic poly(2-vinylpyridine) microgels and anionic polystyrene latex particles have been made by mixing dilute, aqueous suspensions. The growth of the heteroaggregates was arrested by the addition of anionic silica particles that adsorbed to the free surface of the cationic microgel particles. The resulting heteroaggregates were then concentrated by vacuum filtration, freeze-dried, and characterized by mercury porosimetry and electron microscopy. The inclusion of soft, deformable microgels resulted in heteroaggregates with higher porosity than obtained with heteroaggregates of anionic and cationic latex particles. Control of the pore volumes within the freeze-dried filter cakes was demonstrated by two approaches. In the first approach, heteroaggregation at a constant KCl concentration of 0.01 mM was arrested at different times after mixing the latex and microgel particles, thereby limiting the size of the aggregates. The porosity of the resulting filter cake increased from 61 to 65 vol % as the aggregation time increased from 15 to 120 s. In the second technique, the aggregation time prior to arrest was maintained at 120 s while the KCl concentration was varied between 0.01 and 10 mM. The pore volume of the aggregates decreased from 65 to 57 vol % as the electrolyte concentration increased, a trend explained in terms of the effect of the Debye length on the aggregation process.

Journal Article↗

PubMed2005

Small-angle neutron scattering study of concentrated colloidal dispersions: the interparticle interactions between sterically stabilized particles.

Small-angle neutron scattering (SANS) was used to investigate the interparticle interactions in concentrated dispersions of colloidal silica stabilized either by steric or by electrostatic repulsive interactions. In 10 mM NaCl, an adsorbed PEO layer is required to prevent flocculation, and particles are stabilized by steric repulsions. The adsorbed layer was made invisible to neutrons by contrast matching with the aqueous continuous phase. Dispersions of the same particles at the same concentrations but in the absence of added salt and adsorbed PEO were also studied. In both cases, the SANS spectra of concentrated dispersions show a peak at low Q, which is due to interparticle interactions: a structure factor. The SANS data can be described rather well by a homogeneous spherical form factor and a structure factor based on the Hayter-Penfold/Yukawa potential model. The steric potential was compared to the electrostatic potential obtained by fitting the SANS data of the bare silica dispersions. The steric potential shows a greater dependence on the particle volume fraction, which we ascribe to the penetration and compression of the adsorbed PEO layer as the particles approach.

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PubMed2005

Maternal antioxidant supplementation does not reduce the incidence of phenytoin-induced cleft lip and related malformations in rats.

There is considerable evidence that phenytoin-induced birth defects in the rat are a consequence of a period of bradycardia and hypoxia in the embryos. Experiments were designed to test the hypothesis that phenytoin-induced birth defects result from free-radical damage to the embryos during the reoxygenation period posthypoxia. Female rats (>9 per group) were fed either a control diet or a diet high in antioxidants (vitamins C and E and coenzyme Q(10)) both before and during pregnancy and were then given a teratogenic dose of phenytoin (180 mg/kg) on GD 11. The rats were killed on GD 20 and the fetuses were examined for malformations. The initial results showed that the antioxidant diet had a significant protective effect, with far fewer antioxidant-group fetuses showing cleft lip or maxillary hypoplasia compared with the control group. However, this result was confounded by reduced food intake by the rats fed the antioxidant diet and a significantly lower maternal body weight at the time of phenytoin administration. Since the phenytoin was administered by intraperitoneal injection (i.p.) the control rats received higher absolute doses of phenytoin and it is speculated that this results in higher fetal exposure. A second experiment, in which the rats were pair-fed, failed to demonstrate any protective effect of the high antioxidant diet. These results do not support the reoxygenation hypothesis for phenytoin teratogenesis. An alternative explanation would be hypoxia-induced transcription-related changes resulting in cell cycle arrest and apoptosis.

Abnormalities, Drug-Induced↗

PubMed2003

Role of acetylcysteine in the prevention of contrast-media-induced nephrotoxicity.

The role of acetylcysteine in the prevention of contrast-media-induced nephrotoxicity was retrospectively studied. The medical records of patients undergoing cardiac catheterization between January 2000 and March 2002 were reviewed. The outcomes of patients with serum creatinine (SCr) concentrations above 1.2 mg/dL who were undergoing cardiac catheterization with contrast agents and received prophylactic acetylcysteine with i.v. hydration were compared with those of a control group who did not receive acetylcysteine. SCr concentrations were recorded 24 hours before administration of the contrast agent and 48-72 hours afterward for both groups. Sixty patients were included in the study: 32 in the acetylcysteine group and 28 in the control group. Both groups were comparable in demographics, disease states, drug regimens, and risk factors for developing contrast-agent-induced nephrotoxicity. In the acetylcysteine group, the median SCr concentration before receiving the contrast agent was 1.7 mg/dL and remained the same afterward. The median SCr concentration in the control group before administration of the contrast agent and 48-72 hours afterward was 1.6 and 1.9 mg/dL, respectively. The median change in SCr concentrations was greater in the control group than in the acetylcysteine group (0.25 and 0 mg/dL, respectively) (p = 0.001). The percentage of patients developing acute renal failure was greater in the control group than in the treatment group (25% versus 12.5%, respectively) (p = 0.21). The use of prophylactic oral acetylcysteine, combined with i.v. hydration, significantly reduced SCr levels after the administration of contrast media.

Acetylcysteine↗

PubMed2002

Viscosity of colloidal suspensions in aqueous gelatin.

The low-shear viscosity eta(0) of colloidal suspensions of acrylic latex or silica in aqueous gelatin has been measured at a temperature above the sol-gel transition. Measurements were made on dilution of a concentrated suspension with water or a gelatin solution. Thus, either the gelatin : colloid ratio was maintained or it was varied at constant aqueous gelatin concentration. Systems were studied with four lime-processed gelatins of different molecular weights at two concentrations of added salt. In addition, the latex particle size and the thickness of the adsorbed gelatin layer were measured by photon correlation spectroscopy (PCS) under dilute conditions. The dependence of the low-shear viscosity eta(0) on particle concentration was exponential and did not follow the well-established Krieger-Dougherty model for simple hard-sphere suspensions over the concentration range studied. A simple phenomenological model, eta(0)=eta(o)10(phi(e)/phi(s)), was found to predict the behavior well. Here, eta(o) is the viscosity of a gelatin solution of the corresponding solution concentration, phi(e) is proportional to the volume fraction of the particles, and phi(s) is a scaling factor, which was determined to have a value of 0.85. With this value of phi(s), the dimensions determined from PCS could be used to predict the viscosity values.

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