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Heterogeneity of myocardial perfusion in distal coronary embolism with different particle sizes.

BACKGROUND: We hypothesized that altered myocardial perfusion distribution patterns could be seen with coronary distal emboli of different particle sizes using myocardial contrast echocardiography. METHODS: In 16 open-chest anesthetized dogs, microsphere suspensions of 9 or 500 microm in diameter were injected into the left anterior descending coronary artery until the mean left anterior descending coronary artery flow rate was reduced to less than 30% of baseline flow. During baseline conditions and after maximal embolization, real-time myocardial contrast echocardiography was performed by intravenous infusion of an echocontrast agent. RESULTS: In animals infused with 9-microm microspheres, a transmural perfusion defect was seen at the time of maximal embolization. In contrast, in animals infused with 500-microm microspheres, a subendocardial perfusion defect was observed. CONCLUSIONS: The particle size of coronary distal emboli affects myocardial perfusion distribution.

Animals↗

Effect of viscosity and interfacial tension on particle size of cellulose acetate trimellitate microspheres.

The influence of the viscosity of the internal and external phases and the interfacial tension between the two phases, in the emulsion type of microencapsulation system was investigated. The viscosity of mineral oil (external phase) was measured by a capillary viscometer and the viscosity of cellulose acetate trimellitate solution (internal phase) was measured by a Brookfield viscometer. The viscosity of the two phases were measured prior to mixing and at 5 and 60 min after mixing the phases. It was observed that the viscosity of the mineral oil phase prior to mixing had little effect on the average diameter of the microspheres, until a high concentration of light mineral oil was used. A graph of viscosity ratio of the internal phase to the external phase shows that a minimum viscosity ratio may be required before particle size increases. Results are discussed with respect to viscosity effects of mineral oil and polymer solution, as influenced by the solvent uptake by the mineral oil. The interfacial tension between the two phases was measured by pendant drop method. Interfacial tension was measured at 5 and 60 min after the two phases came in contact. The interfacial tension between the mineral oil and polymer solution ranged up to 7 dyne/cm and the particle size was not affected appreciably by the interfacial tension. Particle size and morphological analysis of the microspheres were determined using microscopy and scanning electron microscope.

Benzoates↗

Fracture toughness of resin-modified glass ionomer restorative materials: effect of powder/liquid ratio and powder particle size reduction on fracture toughness.

OBJECTIVES: The objectives of the current investigation were two-fold: (1) to examine the effect of different powder/liquid (P/L) ratios on the fracture toughness of commercial resin-modified glass ionomer cement and conventional glass ionomer cement, and (2) to evaluate the effect of powder size reduction on the fracture toughness of experimental resin-modified glass ionomers in order to improve their physical properties. METHODS: The P/L ratios of the glass ionomer and resin-modified glass ionomers were varied from the manufacturer's recommended ratio to 2.0 and 1.0 by weight. The powder particle sizes for the experimental resin-modified glass ionomers tested were 2, 5, 10 and 25 micro m in diameter. Fracture toughness was determined on ring-shaped specimens with a fatigued pre-crack. RESULTS: The fracture toughness of the resin-modified glass ionomers was significantly higher (p<0.005) than that of the glass ionomer and was not greatly influenced by the P/L ratio. For the experimental resin-modified glass ionomers, it was observed that fracture toughness gradually decreased as the powder particle size became finer. SIGNIFICANCE: The resin components in the liquid play an important role in the improvement of the physical properties of the resin-modified glass ionomer. A reduction in the powder particle size of up to 10 micro m, which resulted in a smoother surface, can maintain high fracture toughness. The high fracture toughness values of the resin-modified glass ionomer may be one of the factors contributing to a favorable clinical outcome in high stress-bearing areas.

Analysis of Variance↗

The particle size distribution, density, and specific surface area of welding fumes from SMAW and GMAW mild and stainless steel consumables.

Particle size distributions were measured for fumes from mild steel (MS) and stainless steel (SS); shielded metal arc welding (SMAW) and gas metal arc welding (GMAW) consumables. Up to six samples of each type of fume were collected in a test chamber using a micro-orifice uniform deposit (cascade) impactor. Bulk samples were collected for bulk fume density and specific surface area analysis. Additional impactor samples were collected using polycarbonate substrates and analyzed for elemental content. The parameters of the underlying mass distributions were estimated using a nonlinear least squares analysis method that fits a smooth curve to the mass fraction distribution histograms of all samples for each type of fume. The mass distributions for all four consumables were unimodal and well described by a lognormal distribution; with the exception of the GMAW-MS and GMAW-SS comparison, they were statistically different. The estimated mass distribution geometric means for the SMAW-MS and SMAW-SS consumables were 0.59 and 0.46 micron aerodynamic equivalent diameter (AED), respectively, and 0.25 micron AED for both the GMAW-MS and GMAW-SS consumables. The bulk fume densities and specific surface areas were similar for the SMAW-MS and SMAW-SS consumables and for the GMAW-MS and GMAW-SS consumables, but differed between SMAW and GMAW. The distribution of metals was similar to the mass distributions. Particle size distributions and physical properties of the fumes were considerably different when categorized by welding method. Within each welding method there was little difference between MS and SS fumes.

Aerosols↗

Comparative evaluation of surfactant and hydrophobizing agent concentration in relation to the optimal particle size of metered-dose inhalers.

The aim of the present study was to formulate stabilized suspension-type metered-dose inhalation aerosols, and to examine the connection between the stabilizing additives and the optimal particle size. For the stabilization of the suspended particles, hydrophilic- and hydrophobic-type additives were applied. Oleil oleate was selected as a hydrophilic anionic surfactant, and the hydrophobizing agent was dimethyl siloxane polymer. The effect of the amount of the applied hydrophilic and hydrophobic additives on the optimal particle size was modeled by a second-order polynomial equation fitted to the data gathered by a face-centered central composite statistical design. We found that if the proper type and amount of additives are selected, it is possible to acquire the therapeutically best composition.

Dose-Response Relationship, Drug↗

Expected particle size distributions of crystals produced from nonisothermal recrystallization.

It is shown, using oxalic acid dihydrate as a model, that nonisothermal recrystallization of powders gives rise to particle size distributions which approach log-normality in many cases. The number of particles formed is, primarily, a function of the nucleation rate constants and the particle size distribution, i.e., the mean diameter and standard deviation are functions of the growth kinetic parameters.

Chemical Phenomena↗

Solubilization of timolol maleate in reversed micellar systems. Measurement of particle size using SAXS and PCS.

Small angle X-ray scattering (SAXS) and photon correlation spectroscopy (PCS) are two methods to measure particle sizes in the order of 10 nm magnitude, which can be used to characterize reversed micellar systems, in this case reverse micelles consisting of lecithin and isopropyl myristate (IPM). In this study these micelles are loaded with different concentrations of the amphiphilic anti-glaucoma drug timolol maleate (TM). The PCS results are consistent with those yielded by SAXS, showing a decrease of particle size with higher TM concentration. In addition, SAXS is capable to give information about the particle shape. This kind of evaluation yields an ellipsoidal shape for micelles with low drug loads, which transform into nearly spherical micelles at higher drug concentrations.

Dose-Response Relationship, Drug↗

Effect of particle size and temperature on the conformation and physiological behavior of apolipoprotein E bound to model lipoprotein particles.

The effect of particle size and structural order/disorder of the lipid domain on the conformation and physiological behavior of lipid-associated apolipoprotein E (apoE) was evaluated. Circular dichroic (CD) spectra of apoE bound to large (LME) and small (SME) microemulsion particles, composed of dimyristoylphosphatidylcholine (DMPC) and cholesteryl oleate (CO), and to DMPC disks revealed that at 4 degrees C, where all of the lipid constituents were in an ordered state, apoE bound to LME displayed approximately 60% alpha-helicity, while apoE bound to SME and DMPC disks displayed 73% and 95% helicity, respectively. Over the temperature range 4-50 degrees C, encompassing the lipid thermal transitions, only apoE bound to LME demonstrated an abrupt change in its CD spectrum (decrease in alpha-helicity) in response to temperature. To determine the source of the abrupt CD change, the constants for dissociation (Kd) of apoE from the surface of the large and small microemulsion particles were determined at 4, 25, and 37 degrees C. These results demonstrated that at 4 degrees C, the KdS for binding of apoE to the LME and SME were approximately equal; however, between 4 and 25 degrees C, there was a 5-fold increase in the Kd for binding of apoE to the LME, whereas the Kd for binding to the SME remained constant. The physiological effects of these differences in apoE secondary structure and equilibrium binding were examined by measuring the capacity of each apoE-containing particle to complete with LDL for binding to human fibroblasts, and by measuring the capacity of the apoE-microemulsion particles to suppress HMG-CoA reductase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins E↗

Study of solid lipid nanoparticles with respect to particle size distribution and drug loading.

This work deals with the formulation and development of Solid Lipid Nanoparticles (SLN) using pressure homogenization technique, nimesulide being used as the model drug. Main emphasis of the work was to study the effect of individual process parameters (homogenization pressure and homogenization cycles) and formulation parameters (lipid concentration and surfactant concentration) on particle size distribution and drug loading. Particle size distribution data indicate that by optimizing the homogenization process and formulation parameters it is possible to produce SLN within a desired size range as required for carrier mediated drug targeting. Approaches to improve drug loading efficiency indicate that drug loading was higher in case of SLN prepared from glyceryl beheanate, palmitostearate and glyceryl tristearate + span 60 as compared to monoacid triglyceride (MAT) tristearate. Thermal analysis by differential scanning calorimetry of the drug loaded SLN indicates the solid nature of the lipid carrier as required for sustained drug release.

Calorimetry, Differential Scanning↗

Effects of feed particle size and feed form on survival of Salmonella typhimurium in the alimentary tract and cecal S. typhimurium reduction in growing broilers.

An in vitro experiment and an in vivo experiment were conducted to investigate the effects of feed particle size (coarse and fine) and feed form (mash and pellet) on the survival of Salmonella typhimurium (ST) in the alimentary tract, and the reduction of cecal ST in growing broilers in a 2 x 2 factorial design. All diets in the 2 trials were corn and soybean meal-based diets that differed only in physical characteristics. Diets were provided for birds from d 1 to 22 of age. In the in vitro trial, the relative gizzard weight was lower in birds that were fed the pellet diet (P < 0.01), whereas the relative weight of the cecum was higher in these birds (P < 0.01). Broilers receiving the pellet diet had enhanced concentrations of volatile fatty acids in contents from both the gizzards and the ceca. In addition, there was an increase in gizzard pH (P < 0.01) with the pellet diet, but a reduction in cecal pH (P < 0.05). Pellet-fed birds showed a significantly decreased and increased in vitro death rate of ST in the contents from gizzards (P < 0.01) and ceca (P < 0.05), respectively. A higher in vitro ST death rate in the gizzard was observed in birds given the coarse mash diet compared with those given the fine mash diet. In the in vivo experiment, cecal volatile fatty acid concentrations were increased, whereas cecal pH was decreased significantly (P < 0.05) when birds were fed the pellet diet compared with the mash diet. Furthermore, cecal ST concentrations were higher (P < 0.05) in broilers fed the pellet diet than in those fed the mash diet. Results indicated that the pellet diet increases the incidence of ST in gizzards and ceca in growing broilers and provide evidence demonstrating that the gizzard may play a critical role in reducing ST contamination in growing broilers.

Animal Feed↗

Association of plasminogen activator inhibitor-1 4G/5G gene polymorphism with variations in the LDL particle size in healthy Japanese men.

BACKGROUND: Several studies have supported the association between a predominance of small, dense low-density lipoprotein (LDL) and the risk of coronary artery disease. As another potentially atherogenic factor, impaired fibrinolytic activity due to increased plasminogen activator inhibitor-1 (PAI-1) concentrations has been shown. In addition, the 4G allele of the 4G/5G polymorphism in the promoter region of the PAI-1 gene is reported to be associated with the atherogenic lipid profile. We investigated the relation between the PAI-1 gene polymorphism and LDL particle size. METHODS: A total of 156 healthy Japanese male subjects were recruited. The diameter of LDL particles was determined at their peak size using polyacrylamide gels using fresh plasma samples. RESULTS: Fasting insulin and triglyceride concentrations were found to be significantly higher, and the LDL particle size was smaller in the homozygotes for the 5G allele than in the carriers of the 4G allele. An analysis of covariance (ANCOVA) adjusting for insulin and triglyceride concentrations showed a consistently significant difference in LDL particle size between the two groups. In the forward stepwise multiple regression analysis, triglycerides, insulin, and the PAI-1 5G/5G genotype remained in the model as independent and significant predictors capable of influencing the LDL particle size. CONCLUSIONS: Our findings suggest that the 4G/5G polymorphism of the PAI-1 gene might be associated with LDL particle size in healthy Japanese males.

Adult↗

Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs.

This study evaluated cellular uptake of polymeric nanoparticles by using Caco-2 cells, a human colon adenocarcinoma cell line, as an in vitro model with the aim to apply nanoparticles of biodegradable polymers for oral chemotherapy. The feasibility was demonstrated by showing the localization and quantification of the cell uptake of fluorescent polystyrene nanoparticles of standard size and poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with polyvinyl alcohol (PVA) or vitamin E TPGS. Coumarin-6 loaded PLGA nanoparticles were prepared by a modified solvent extraction/evaporation method and characterized by laser light scattering for size and size distribution, scanning electron microscopy (SEM) for surface morphology, zeta-potential for surface charge, and spectrofluorometry for fluorescent molecule release from the nanoparticles. The effects of particle size and particle surface coating on the cellular uptake of the nanoparticles were quantified by spectrofluorometric measurement. Cellular uptake of vitamin E TPGS-coated PLGA nanoparticles showed 1.4 folds higher than that of PVA-coated PLGA nanoparticles and 4-6 folds higher than that of nude polystyrene nanoparticles. Images of confocal laser scanning microscopy, cryo-SEM and transmission electron microscopy clearly evidenced the internalization of nanoparticles by the Caco-2 cells, showing that surface modification of PLGA nanoparticles with vitamin E TPGS notably improved the cellular uptake. It is highly feasible for nanoparticles of biodegradable polymers to be applied to promote oral chemotherapy.

Administration, Oral↗

Effect of particle size on the pharmacokinetics of menatetrenone incorporated in O/W lipid emulsions prepared with hydrogenated castor oils and soybean oil in rats.

Previously, we prepared lipid emulsions with soybean oil (SO; 20%) as oil phase and hydrogenated castor oils (HCOs; 2.4%) as emulsifiers (SO(20)/HCOs(2.4)), and found that the lipid emulsions prepared with HCO of 10 oxyethylene units (SO(20)/HCO10(2.4)) were quickly cleared from the plasma, while those prepared with HCO of 20 oxyethylene units (SO(20)/HCO20(2.4)) showed prolonged plasma circulation of the incorporated drug (Ueda et al., 2003). In the present study, the pharmacokinetics of menatetrenone incorporated into SO/HCO10s and SO/HCO20s of different particle sizes (100-280 nm), obtained by altering the SO contents, were examined in rats. The plasma half-lives of menatetrenone as SO/HCO10s were similar to each other, irrespective of particle size, even though the liver uptake of menatetrenone as SO(2.5)/HCO10(2.4) was larger than that as SO(20)/HCO10(2.4). The menatetrenone half-lives were also similar to each other for SO/HCO20s. The pretreatment with dextran sulfate 500,000 (DS500), a suppressor of the reticuloendothelial system (RES), increased the plasma concentration and inhibited the liver uptake of menatetrenone as SO/HCO10s, but not for those as SO/HCO20s. These findings indicated that the particle sizes did not affect the minimum oxyethylene units within HCOs for the prolonged plasma circulation of menatetrenone as SO/HCOs, which was 20.

Animals↗

Lasalocid and particle size of corn grain for dairy cows in early lactation. 2. Effect on ruminal measurements and feeding behavior.

The effects particle size of corn grain and the ionophore lasalocid on ruminal fermentation and feeding behavior of early lactation cows were examined. Eight multiparous and 4 primiparous cows in early lactation were fed diets (44% forage) with cracked or ground dried shelled corn grain and with or without lasalocid (360 mg/d per cow). The experiment was a replicated (n = 3) 4 x 4 Latin square design with 21-d periods and a 2 x 2 factorial arrangement of treatments. Ground corn decreased ruminal turnover time of starch, did not affect ruminal lactate concentrations, increased propionate, decreased the ratio of acetate to propionate, and decreased branched-chain fatty acids. The range of ruminal pH within a day increased with ground corn, but mean pH was unaffected by treatment. Lasalocid increased lactate concentrations and did not affect the ratio of acetate to propionate. Lasalocid increased total time spent ruminating, and ground corn decreased ruminal contractions. Lasalocid tended to increase water intake, and ground corn increased water intake. Interactions of lasalocid and particle size of the corn grain were observed for ruminal turnover time of starch and NDF, and ruminal pool size of acetate and total VFA.

Acetates↗

Evaluation of the Malvern Spraytec with inhalation cell for the measurement of particle size distribution from metered dose inhalers.

The purpose of this study was to evaluate the Malvern Spraytec with inhalation cell attachment as a means of analyzing the particle size distribution of aerosols from pressurized metered dose inhalers (pMDIs). The aerosol particle size distribution of various commercially available, placebo, and experimental pMDI formulations was determined using Spraytec under various experimental conditions and the relevant data were compared with the Andersen cascade impactor data. The Spraytec volume median diameter (Dv 50) values for commercial chlorofluorocarbon- and hydrofluoroalkane (HFA)-based pMDIs were respectively smaller and higher compared with their reported mass median aerodynamic diameter values. It was possible to obtain a close agreement between Spraytec Dv 50 and the reported mass median aerodynamic diameter values for a solution-type pMDI formulation, Qvar 50, by equilibrating the pMDI to 55 degrees C before the measurement and using a 20-cm throat extension. Incorporation of a nonvolatile solvent propylene glycol (PG) in placebo pMDIs (15% w/w ethanol, 0.5-20.0% w/w PG in HFA 134a) showed an increase in Dv 50 with increasing concentration of PG. Furthermore, it was possible to obtain a correlation (R(2) = 0.8037) between Spraytec and Andersen cascade impactor data for the experimental nimesulide-pMDI formulations containing 0.1% w/w drug, 0.25-10% w/w PG, and 15% ethanol in HFA 134a.

Aerosols↗

Influence of molecular structure on sorption of phenoxyalkanoic herbicides on soil and its particle size fractions.

The sorption and desorption behaviors of four phenoxyalkanoic acid herbicides and their metabolites on four agricultural soils and soil particle size fractions were examined. Generally, there was a trend of increasing adsorption and decreasing desorption in the order mecoprop < MCPA < dichlorprop < 2,4-D. The significant increase in adsorption of the phenolic metabolites can be explained by their lower polarity and enhanced partition in the organic soil matrix. Estimation of sorption distribution coefficients from particle size fraction adsorption data was possible for a sandy soil and a silty Cambisol soil only. It is suggested that increasing steric demand, for example, molecular volume, and slight changes in the polarity of the compounds affect their adsorption properties. Comparison of adsorption and desorption data of structurally similar compounds obtained from a variety of soils allows investigation of structure-induced differences in sorption strength.

Adsorption↗

Significance of particle size of benzo(a)pyrene for the induction of respiratory tract tumours in hamsters.

To study the role of particle size of benzo(a)pyrene (BP) in the induction of respiratory tract tumours, goups of hamsters were given 52 weekly intratracheal instillation of fine (77% less than 5.2 micron; 3% less than 1.3 micron) or coarse (77 less than 42 micron; 0% less than 10 micron) BP particles suspended in gelatin-0.9% NaCl solution. Both the fine and coarse particles were given at two different dose levels, viz., 0.5 and 1.0 mg BP/instillation. Another group of hamsters received 52 weekly intratracheal instillations each consisting of 1.0 mg BP particles of a wide size range (90% less than 50 micron; 3% less than 5.0 micron) suspended in 0.9% NaCl solution without gelatin. The retention of BP in the respiratory tract was studied in separate groups of hamsters receiving a single instillation of BP particles of the different size ranges. Coarse BP particles cleared less rapidly from the lungs and induced a much stronger tumour response in the respiratory tract than did fine BP particles. These findings demonstrated the crucial significantce of particle size for the effectiveness of BP as a respiratory tract carcinogen. No appreciable differences in site of tumour formation were observed between treatment with fine and coarse BP particles, which led to the conclusion that the size of the particles did not play an important role in determining the location of the induced respiratroy tract tumours. The elimination rate of the BP particles with a wide size range appeared to be in between those of the fine and the coarse particles. The tumour response found after administration of the BP particles of wide size range was very similar to that obtained with the high dose of coarse PB particles.

Animals↗

Introduction of poly-L-lactic acid microspheres into the skin using supersonic flow: effects of helium gas pressure, particle size and microparticle dose on the amount introduced into hairless rat skin.

A microparticulate bombardment system loaded with DNA- and RNA-coated gold and tungsten microparticles (diameter 1-3 microm; density about 19 g cm(-3)), the Helios gene gun system (Helios gun system), has been used to deliver a gene into cells by accelerating the microparticles to high velocity using a supersonic flow of helium gas. To investigate whether drug-loaded microspheres, > 20 microm in diameter and about 1.0 g cm(-3) in density, could be delivered in powder form quantitatively into the skin using the Helios gun system equipped with a cartridge container fitted with a rupture membrane, we investigated the effect of the helium gas pressure in accelerating indometacin-loaded poly-L-lactic acid (PLA) microspheres, as well as the particle size and the bombardment dose on delivery into the skin. Introduction of indometacin (i.e. indometacin-loaded PLA microspheres) after bombardment, with 3.0 mg indometacin-loaded PLA microspheres of a particle size of 20-38, 44-53 and 75-100 microm at a helium pressure of 100, 200 and 300 psi, of the abdomen of hairless rats increased in parallel with the helium pressure and it was also affected by the particle size, being highest at a diameter of 75-100 microm. However, introduction of higher amounts of PLA microspheres resulted in more severe skin erythema (skin damage) as monitored by the Draize score. Using lower bombardment doses (0.5 and 1.0 mg), the efficiency of introduction was improved and the skin damage markedly reduced. Moreover, discrete bombardment with a low dose provided a more efficient introduction of indometacin and less skin damage. These results suggest that bombardment injection of drug-loaded microspheres in a powdered form by the Helios gun system appears to be a very useful tool for the quantitative delivery of a variety of drugs and an alternative to parenteral injection by needle, especially for delivering water-soluble macromolecules.

Animals↗