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At least 433 records · Page 24Linked to original sources

PubMed2005

PLA-PEG particles as nasal protein carriers: the influence of the particle size.

Previous studies have shown that PLA-PEG nanoparticles (NP) are able to enhance the transport of the encapsulated model protein, tetanus toxoid (TT), across the rat nasal mucosa. The aim of this work was to study if the size of PLA-PEG particles affects the nasal transport of the encapsulated protein and, also, the potential contribution of blank nanoparticles to the transport of the free protein. To achieve this purpose, 125I-TT was encapsulated into PLA-PEG particles of different sizes (200 nm, 1.5, 5 and 10 microm) prepared by the water-in-oil-in-water solvent evaporation technique. Firstly, in order to investigate the carrier role of the particles, two series of either conscious or anaesthetized rats were nasally treated with 125I-TT-loaded NP, free 125I-TT, and a physical mixture of blank NP and free 125I-TT. Secondly, the influence of the particle size on the nasal transport of TT encapsulated into PLA-PEG particles was evaluated in conscious rats. The amount of radioactivity recovered in the blood compartment, lymph nodes and other relevant tissues was monitored for up to 24h. Finally, the nasal bioavailability of 125I-TT-loaded PLA-PEG NP was calculated. The results indicated that the use of anaesthesia enhances the transport of 125I-TT and that the physical presence of PLA-PEG NP does not affect the transport of the toxoid. In contrast, when TT was encapsulated into the particles its transport across the nasal mucosa of conscious rats was significantly enhanced. Furthermore, the efficacy of this transport was related to the particle size, reaching the most important transport for the smallest particle size. The intensity of this transport was also illustrated by the high nasal bioavailability of TT encapsulated into nanoparticles (200 nm) (F = 70-80%). These results led us to conclude that PLA-PEG NP can be accepted as nasal protein carriers for nasal administration.

Administration, Intranasal↗

PubMed2000

Cellular cholesterol efflux in heterozygotes for tangier disease is markedly reduced and correlates with high density lipoprotein cholesterol concentration and particle size.

Tangier disease (TD), caused by mutations in the ATP-binding cassette 1 (ABC-1) gene, is a rare genetic disorder characterized by severe deficiency of high density lipoproteins (HDL) in the plasma, hypercatabolism of HDL, and defective apolipoprotein (apo)-mediated cellular cholesterol efflux. In the present study, we assessed plasma lipid concentrations, HDL particle size and subspecies, and cellular cholesterol efflux in 9 TD heterozygotes from a kindred in which the proband was homozygous for an A-->C missense mutation at nucleotide 5338 of the ABC-1 transcript. Relative to age- and gender-matched controls from the Framingham Offspring Study (FOS), TD heterozygotes had significant reductions (P < 0.000) in HDL-C (-54% female; -40% male) and apoA-I (-33% female; -37% male) concentrations, as well as significantly less cholesterol (-68% female; -58% male) distributed in the largest HDL subclasses, H5 and H4. Consequently, HDL particle size (nm) was significantly smaller (P < 0.000) in TD heterozygotes (8.6 +/- 0.6 female; 8.7 +/- 0.1 male) relative to FOS controls (9.4 +/- 0.4 female; 9.0 +/- 0.3 male). Further studies demonstrated that apoA-I-mediated cellular cholesterol efflux in TD heterozygotes was essentially half that of controls (11 +/- 2 vs. 20 +/- 3% of total [(3)H]cholesterol, P < 0. 001), with strong correlations observed between cholesterol efflux and both HDL-C level (r = 0.600) and particle size (r = 0.680). In summary, our data demonstrate that apolipoprotein-mediated cholesterol efflux is aberrant in TD heterozygotes, as it is in homozygotes. This finding, along with the associations observed between HDL-C concentration, HDL particle size, and cholesterol efflux, supports the concept that plasma HDL-C levels are regulated, in part, by cholesterol efflux, which in turn influences HDL particle size and, ultimately, HDL apoA-I catabolism.

ATP Binding Cassette Transporter 1↗

PubMed1997

Optimum particle size distribution for reduced sintering shrinkage of a dental porcelain.

OBJECTIVES: The purpose of this investigation was to develop a systematic method for obtaining an optimum particle size distribution for a given dental porcelain and compaction method that had a low sintering shrinkage. METHODS: Particles of coarse, medium and fine size were obtained from a commercial dental porcelain using a sedimentation method. Particle sizes were chosen so that the smaller particles would fit into the interstices between the next larger size. The different-sized powders were mixed in various proportions and compacted into a cylindrical mold. The specimens were fired and their linear firing shrinkages determined. An equation was developed to predict optimum proportions. The shrinkage of these mixed powders was compared to the shrinkage of the component powders, to the as-received commercial porcelain, and to predictions based on theoretical equations. These comparisons were statistically analyzed using analysis of variance (ANOVA) and Fisher's Protected Least Significant Differences (PLSD). RESULTS: Mixing specific proporations of different-sized particles significantly reduced sintering shrinkage (p = 0.01) for all mixtures except for one trimodal mixture having the smallest particles. These reductions in shrinkage were obtained for the proportions predicted by the developed equation. Sintering shrinkages for predicted proportions of a three-component mixture and two two-component mixtures were significantly less than that of the original powder (p = 0.01). SIGNIFICANCE: A systematic method was developed for producing dental frits with low firing shrinkage. Mixing of different-sized particles produced frits with lower sintering shrinkage. The optimum proportions of the sized particles were given by an equation. The results of this study suggest that optimum particle size distributions for frits are dependent upon compaction methods.

Aluminum Silicates↗

PubMed2006

Particle size limits to meet USP content uniformity criteria for tablets and capsules.

Content uniformity (CU) of pharmaceutical dosage units can be affected by active pharmaceutical ingredient (API) particle size and size distribution. Previous authors have estimated this impact but use of different particle size descriptors led to confusion and difficulty in applying the theoretical models developed. We show that when the same descriptors for particle size and distribution are used (i.e., median diameter on a weight basis (d(50)) and geometric standard deviation (sigma(g))), previously published models are consistent. The approach of Yalkowsky and Bolton4 [Pharm Res 7:962-966, 1990] is modified to use these descriptors and updated for current USP28/NF23 CU criteria. A nomograph is provided to allow easy estimation of an acceptable d(50) for a given dose and sigma(g). To test the model's validity, tablets were manufactured over a wide range of doses and assayed for CU. As predicted, %relative standard deviation (RSD) increased as dose decreased. However, for APIs that deviate significantly from the assumed log-normal distribution, sigma(g) is more appropriately described by the upper region of the API size distribution, presumably because large particles have greatest influence on CU. At very low doses, CU values deviate significantly from normality, consistent with the presence of single large API particles causing super-potent dosage units.

Algorithms↗

PubMed2004

Studies of LDL particle size and susceptibility to oxidation and association with glucose metabolism in children after heart transplantation.

BACKGROUND: Increased concentrations of serum triglyceride and low-density lipoprotein (LDL) cholesterol are common after heart transplantation (HTx). These abnormalities may promote transplant vascular disease and atherosclerosis, especially if LDL is small, dense, and oxidized. There have been no previous studies of LDL particle size and LDL susceptibility to oxidation in children after HTx. METHODS: Twenty-three HTx recipients (aged 3-19 years) who received triple-drug immunosuppression therapy after HTx and 181 controls within the same age range participated in the study. Total, high-density lipoprotein, and LDL-cholesterol concentrations; triglyceride concentration, and glucose and insulin concentrations during oral glucose tolerance tests were determined an average of 3 years after HTx (range, 1-7 years). Moreover, we determined serum lipoprotein (a) concentration, apolipoprotein E phenotype, LDL particle size, and indices of LDL susceptibility to copper-induced oxidation in 12 HTx recipients. RESULTS: We found hypertriglyceridemia in 56.5% and hyperinsulinemia in 30.4% of patients. Triglyceride concentration and body mass index were associated significantly with insulin concentration (p < 0.008 for both). Low-density lipoprotein particle size, LDL susceptibility to in vitro oxidation, and lipoprotein (a) concentrations did not differ significantly between HTx patients and controls. Low-density lipoprotein particle size was associated inversely with cyclosporine through level (Neoral, r = -0.59, p = 0.045), whereas weight-adjusted dosage of cyclosporine correlated positively with longer lag time of LDL oxidation (r = 0.69, p = 0.013). CONCLUSIONS: Hypertriglyceridemia and hyperinsulinemia were common in children receiving triple-drug immunosuppression therapy after HTx. Increased cyclosporine through concentration was associated with small LDL particle size but did not increase LDL susceptibility to oxidation.

Adolescent↗

PubMed2003

The effect of particle size and electrical charge on macrophage-osteoclast differentiation and bone resorption.

In aseptic loosening, there is commonly periprosthetic bone loss and a heavy macrophage infiltrate in response to biomaterial wear particles generated from the implant materials. Macrophages which have phagocytosed wear particles are known to be capable of differentiation into bone resorbing osteoclasts. In this investigation we determine the role of particle size and particle charge on this process. Mouse monocytes and macrophages were co-cultured with osteoblast-like UMR106 cells and 1,25 dihydroxyvitamin D3 in the presence or the absence of (i) various sizes of latex beads (0.1, 1, 10 and 100 microm) and (ii) uncharged, positively- or negatively-charged sephadex beads of uniform shape and composition. The extent of osteoclast differentiation by monocytes or foreign body macrophages was determined by the expression of the osteoclast-associated enzyme tartrate-resistant acid phosphatase and lacunar bone resorption. No significant difference in the extent of osteoclast formation and bone resorption was noted in response to particle size. Osteoclast formation was also not significantly different in the presence of positively/negatively charged and uncharged particles. These findings indicate that osteoclast formation is not significantly influenced by particle characteristics, such as particle size. They also add support to the hypothesis that macrophage involvement in periprosthetic osteolysis is not dependent on particle phagocytosis and that it may be induced by particle contact.

Journal Article↗

PubMed1986

Increases in the particle size of high-density lipoproteins induced by purified lecithin: cholesterol acyltransferase: effect of low-density lipoproteins.

Homogeneous subpopulations of human high-density lipoproteins subfraction-3 (HDL3) have been incubated at 37 degrees C with purified lecithin: cholesterol acyltransferase, human serum albumin and varying concentrations of human low-density lipoproteins (LDL). Changes in HDL particle size and composition during these incubations were monitored. Incubation of HDL3a (particle radius 4.3 nm) in the absence of LDL resulted in an esterification of more than 70% of the HDL free cholesterol after 24 h of incubation. This, however, was sufficient to increase the HDL cholesteryl ester by less than 10% and was not accompanied by any change in particle size. When this mixture was incubated in the presence of progressively increasing concentrations of LDL, which donated free cholesterol to the HDL, the molar rate of production of cholesteryl ester was much greater; at the highest LDL concentration HDL cholesteryl ester content was almost doubled after 24 h and there was an increase in the HDL particle size up to the HDL2 range. In the case of HDL3b (radius 3.9 nm), there were again only minimal changes in particle size in incubations not containing LDL. In the presence of the highest concentration of LDL tested, however, the particles were again enlarged into the HDL2 size range after 24 h incubation. These HDL2-like particles were markedly enriched with cholesteryl ester but depleted of phospholipid and free cholesterol when compared with native HDL2. Furthermore, the ratio of apolipoprotein A-I to apolipoprotein A-II resembled that in the parent-HDL3 and was very much lower than that in native HDL2. It has been concluded that purified lecithin: cholesterol acyltransferase is capable of increasing the size of HDL3 towards that of HDL2 but that other factors must operate in vivo to modulate the chemical composition of the enlarged particles.

Adult↗

PubMed2001

Why particle size should affect clinical response to inhaled therapy.

Studies with beta2-adrenergic agonists have shown that particle size and total dose are important determinants of optimum bronchodilation. Drug deposition in the airways is probably the most important factor for bronchodilation, since beta2-adrenoceptors and muscarinic M3 receptors are present mainly in the peripheral and central airways, respectively. Furthermore, clinical efficacy can be maintained while minimizing systemic exposure by selecting an appropriate particle size. Changes in lung function provide a means of monitoring the relationship between delivery of the bronchodilator and its efficacy, whereas there is no such immediate means of assessing antiinflammatory preventative therapy such as inhaled corticosteroids. Asthma is primarily an inflammatory disease but there are no simple tests to detect the accumulation of inflammatory cells and mediators. Data are presented to demonstrate the reduction of certain inflammatory markers in bronchial biopsy tissue taken from asthmatic patients after corticosteroid therapy. Measurement of inflammatory markers in both bronchial biopsy tissue and bronchoalveolar lavage samples may provide a way of monitoring the site of action and efficacy of inhaled corticosteroids in the future. Furthermore, it is envisaged that the effect of corticosteroid particle size on efficacy and systemic bioavailability may be investigated by exploiting these methods.

Administration, Inhalation↗

PubMedDate not supplied

Estimation of subcellular particle size histograms with electron microscopy for prediction of optical scattering in breast tissue.

Diffuse near-infrared tomography of tissue reveals scattering changes that originate from the submicroscopic features of the tissue; yet the existing tools to use this information to predict which features contribute to the scattering spectrum are limited by the lack of direct data quantifying the particle sizes. Breast tissue was examined with electron microscopy, and analysis showed that the distributions of particle sizes appear in double exponential functions for most cellular tissues. The average particle size histograms of high-grade cancer, low-grade cancer, fibroglandular tissue, and adipose tissue were examined. The particle histograms were progressively decreasing in magnitude for these tissue types, and the average size of the particles increased, for these four tissues, respectively. Typical particle sizes in the range of 10 to 500 nm for these tissue types, with biexponential fitting, gave two particle distributions: one near 20 to 25 nm for the smaller size and one at 110 to 230 nm for the larger distributions. Mie scatter theory was used to take these particle distributions and calculate scattering spectra. The ability to image reduced scattering coefficient spectra of bulk breast tissues exists, and so this data provides insight into how bulk imaging may be mapped over to predict factors related to the tissue ultrastructure.

Breast↗

PubMed2005

Use of the next generation pharmaceutical impactor for particle size distribution measurements of live viral aerosol vaccines.

Aerosol administration of live measles vaccine virus has proven to be extremely efficacious in field trials using an industrial compressor coupled to a disposable nebulizer (IPI). To develop a new system for administration, it is necessary to characterize the operating characteristics of the old system. There are no standardized techniques for measuring particle size of live biological agents. This study evaluated the Next Generation Pharmaceutical Impactor's (NGI) ability to particle size wet aerosols in an effort to measure the particle size distribution of live measles vaccine from the IPI nebulizer. As a control albuterol was aerosolized using a Pari LC Star, since the soluble albuterol is evenly distributed throughout the droplets and laser diffraction measurements should agree with those from the NGI, as long as the NGI is cooled to prevent heat transfer to the aerosol. Albuterol was also used as a control for the IPI using quantitative ultraviolet spectrophotometry. There was close agreement in MMD (mean +/- 95% CI) for the LC Star, measured by laser diffraction (3.24 +/- 0.06 microm) and the NGI (2.93 +/- 0.22 microm) and the IPI (4.26 +/- 0.17 and 4.26 +/- 0.24 microm, respectively). For the measles vaccine assayed for plaque forming units, there were significant differences between the NGI MMD (6.14 +/- 0.39 microm) compared to laser diffraction (4.95 +/- 0.16 microm) indicating that the vaccine is not evenly distributed among the droplets of various sizes. This is likely clumping of the virus due to gelatin in the formulation. These data indicate that the NGI is capable of particle sizing live biological agents.

Administration, Inhalation↗

PubMed2003

Induced-sputum particle size distribution and pulmonary function in foundry workers.

The authors studied and determined a correlation between the distribution of particle size in induced sputum and pulmonary function tests among 54 foundry workers, of whom 34 had been exposed to a variety of metals. Sputum was induced with an ultrasonic nebulizer and processed by conventional methods; a particle scanner was used to measure particle size. All participants underwent spirometry to measure their flow rates. There were significant differences between the exposed and nonexposed groups with respect to the proportion of particles with diameters greater than 2 microm and with diameters greater than 5 microm. A positive correlation was found between the proportion of particles greater than 5 microm in diameter and the ratio of forced expiratory volume in 1 sec (FEV1.0) to forced vital capacity (FVC) (i.e., FEV1.0/FVC) for all 54 workers, and there was a significant correlation for non-smokers. Correlations by work categories revealed a significant negative correlation among casting workers between particles with diameters greater than 5 microm and percentage of FVC. These findings indicate the value of measuring particle size in induced-sputum specimens as a tool for differentiating between exposed and nonexposed workers. Also indicated was a tendency toward a restrictive pattern in pulmonary function tests among workers who had exposure to higher percentages of large particles.

Adult↗

PubMed1990

Influence of forage diets on ruminal particle size, passage of digesta, feed intake and digestibility by steers.

To assess the influence of forage diets on particle size of digesta in the rumen, three ruminally fistulated steers were fed alfalfa, orchardgrass or switchgrass hays in a 3 x 3 Latin square design. Mean sieve size of ruminal digesta for alfalfa, orchardgrass and switchgrass diets was 671, 652 and 466 microns, respectively. A second experiment examined the influence of ruminal particle size on digesta passage, digestibility and intake. Four ruminally fistulated Angus-Hereford steers were given ad libitum access to different proportions of alfalfa and switchgrass in a 4 x 4 Latin square design. Either a 100% alfalfa, 50% alfalfa:50% switchgrass, 25% alfalfa:75% switchgrass or 100% switchgrass diet was offered once daily. Mean sieve sizes of the ruminal digesta of these diets responded cubically (P less than .01; 1,066, 946, 1,003 and 925 microns, respectively). Mean ruminal turnover times were 24.3, 24.8, 24.7 and 29.8 h, respectively. Dry matter intake increased linearly (P less than .10) as the proportion of legume in the diet increased; no influence of diet on DM digestibility was observed. Passage rate of dosed nylon particles 1, 3 and 5 mm in length was influenced (P less than .01) by size; however, no difference in the passage rates of the nylon particles due to diet was evident. Particle size of ruminal digesta did not respond in a linear manner to the proportion of legume in the diet. A smaller ruminal particle size was not associated with a faster turnover of digesta.

Animal Feed↗

PubMed2001

Change in the particle size distribution of poly (L-lactide) wear debris by gamma-ray irradiation.

It has been known that the wear debris causes failure of implant prostheses. In this study, the convenient wear test of poly(L-lactide) (PLLA) was established and the particle size of PLLA wear debris was analyzed using the Coulter counter. Then, the changes in the particle size distribution of PLLA wear debris by gamma-ray irradiation were observed dose-dependently at the dose of 10, 25 and 50 kGy. With the increasing irradiation dose, the particle size distribution of PLLA wear debris shifted toward the smaller diameter size, and the mean diameter of PLLA wear debris significantly decreased. In addition, the tensile strength and the molecular weight of irradiated PLLA were also decreased by increasing the irradiation dose. The lowering of the molecular weight by gamma-irradiation resultingly caused the decreases in tensile strength of irradiated PLLA and the particle size of the wear debris derived from irradiated PLLA.

Biocompatible Materials↗

PubMedDate not supplied

Biomass and aggregation analysis of human embryonic kidney 293 suspension cell cultures by particle size measurement.

A method has been developed to monitor the cell growth of aggregated human embryonic kidney 293 (HEK293) suspension cultures by measuring cumulative particle volume and the particle size distribution. This method employs a particle size analyzer that determines the size of individual particles by detecting their light obscuration (blockage) or scattering. Cell counts derived from the cumulative volume of the cell particle correlate well with manual cell counts from a hemacytometer at different stages of growth. This correlation was further confirmed by quantifying total cellular protein of the samples. Simultaneously, the aggregation state of the samples can also be monitored and mathematically described. Results from this study demonstrate that this simple and reproducible method allows the direct measurement of cumulative cell volume and the degree of cell aggregation, as well as an indirect assessment of cell counts.

Biomass↗

PubMed1995

Relationship of low-density lipoprotein particle size to plasma lipoproteins, obesity, and insulin resistance in Japanese men.

OBJECTIVE: To determine the clinical characteristics of patients with small low-density lipoprotein (LDL) particles among Japanese men with mild glucose intolerance and to investigate the relationship of LDL particle size to the levels of other plasma lipoproteins, obesity, insulin resistance, and blood pressure (BP). RESEARCH DESIGN AND METHODS: The subjects were 40 men with impaired glucose tolerance or diabetes treated by diet alone, and 40 healthy men matched for age and body mass index (BMI) were used as control subjects. LDL particle size was measured using gradient gel electrophoresis. RESULTS: Of the 40 patients with glucose intolerance, 19 had small LDL (particle size < 25.5 nm) compared with only 4 of the 40 control subjects. In the patients with small LDL, the plasma levels of cholesterol, triglycerides, and apolipoprotein B, the fasting serum immunoreactive insulin, and the waist-to-hip ratio were all higher than in the patients with normal LDL (particle size > or = 25.5 nm), while the high-density lipoprotein cholesterol level was lower. However, there were no significant differences in BMI, BP, or insulin sensitivity in a euglycemic clamp study between the small-LDL and normal-LDL subgroups. CONCLUSIONS: Japanese men with glucose intolerance frequently have small LDL, and this abnormality is associated with other dyslipoproteinemias and increased waist-to-hip ratio.

Aged↗

PubMed2006

Effect of rostrocaudal mobility of the mandible on feed digestibility and fecal particle size in horses.

OBJECTIVE: To evaluate the effect of rostrocaudal mobility (RCM) of the mandible during extension and flexion of the atlanto-occipital joint on weight gain, feed digestibility, and fecal particle size in horses. DESIGN: Randomized controlled trial. ANIMALS: 34 pregnant mares housed in 1 barn. PROCEDURES: Horses were randomized into a treatment (n = 17) or control (17) group. All horses were sedated, and the distance between the rostral portions of the upper and lower incisor arcades was determined during extension and flexion of the atlanto-occipital joint; mandibular RCM was calculated as the difference between these values. In the treatment group, measurements were made after dental floating. Body weight was recorded 1 day before dental floating and at intervals after mandibular RCM determination for a period of 24 weeks. Feces were collected from each horse during two 5-day periods. Samples of feed and feces were analyzed to determine feed digestibility; particle size analysis was performed on dried fecal samples. RESULTS: Data obtained from each group of horses revealed that RCM of the mandible did not affect weight gain, feed digestibility, or particle size in feces; there were no differences among breeds. Controlling for age and number of dental lesions did not significantly affect results. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, RCM of the mandible did not appear to affect weight gain, feed digestibility, or fecal particle size. On the basis of these and other published data, the assumption that dental abnormalities affect digestion detrimentally in horses needs to be reevaluated.

Animals↗

PubMed1980

Dependence of area under the curve on proquazone particle size and in vitro dissolution rate.

The in vitro dissolution and GI absorption of various sieve fractions of proquazone were studied (particle-size ranges of 45-74, 160-300, and 500-1000 micrometer). The dissolution rates of preparations F45, F160, and F500 were determined in vitro in a flow-through assembly in artificial gastric juice at 37 degrees. The time required for 63% of the maximum amount of soluble drug to pass into solution was characterized by the dissolution variable tau D. The in vitro dissolution rates for the preparations differed significantly in the order tau D, F45 less than tau D, F160 less than tau D, F500. After oral administration of 300 mg of the fractions to each of eight rhesus monkeys, the area under the plasma level-time curve (AUC) differed significantly in the order AUC F45 greater than AUC F160 greater than AUC F500. The dissolution rate increased with decreasing particle size. The AUC increased with decreasing particle size and with increasing dissolution rate. These results indicate that the dissolution rate probably determines the extent of absorption when dissolution is rate limiting.

Animals↗

PubMed1999

Particle size distributions in mesh cuts and microscopically estimated volumetric shape factors.

When particle size distribution parameters are calculated from sieve analysis, it is generally assumed that the distribution within the particle cut is either linear, producing a mean particle size equal to the average of the mesh openings (1-3), or that a more proper number is the geometric mean of these two apertures. It is shown here that particles within a mesh cut are not linearly distributed, but rather may be normally, long-normally, or biphasic combinations of the two. Three compounds were examined in this fashion, and results are reported here.

Algorithms↗