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PubMed1996

Interrelationship between buffer systems and particle sizes of TCPL drug delivery system.

The specific objective of this investigation is to study the effect of tricalcium phosphate delivery system (TCPL) particle sizes on the final density as well as the delivery profiles of various organic compounds in three different buffer environments. Each TCPL matrices were fabricated using three different particle sizes ranges between 1-38, 45-63 and 63-75 microns. The sintered microcrystal material was impregnated with either progesterone (P, 100 mg each) or bovine serum albumin (BSA, 100 mg each). In phase I of the study, each device was suspended in a serum bottle containing 100 mls of ethanol solution (50% wt/vol.) for P release or 100 mls of PBS (pH 7.4) for BSA release. In phase II, similar capsules were suspended in human plasma instead of standard buffers. The vials were agitated at 100 cycle per minute in a water bath set at 37 degrees C. The amount of P or BSA released from the devices into the buffered medium was measured spectrophotometrically. The results of this investigation revealed that a significant difference in the densities of the devices made from the range of individual particle sizes. The rate of steroid hormone and protein released from the devices made from 1-38 micron particle sizes was slower (p < 0.05) than the rate of delivery of P and BSA released from devices fabricated from either 45-63 or 63-75 micron particles. Regardless of the particle sizes effect the results show that the delivery profiles of BSA was higher than the rate of P. This observation could be attributed to the molecular structure as well as the physiochemical characteristics of the drug. In conclusion the data obtained from this study suggest that: (1) Particle sizes variations influence the density of the TCPL delivery system, (2) the rate of release of organic compounds from the ceramic devices is considerably affected by the physiochemical characteristics of medium or buffer system, and (3) the delivery rate of drugs from TCPL devices is directly proportional to the size of the device initial particles and macropores, and inversely proportional to the number of micropores within each device.

Buffers↗

PubMed1986

Dependence of pulmonary absorption kinetics on aerosol particle size.

To determine the effect of aerosol particle size upon absorption from the respiratory tract (RT), solid, polydisperse disodium fluorescein aerosols (MMDae 1.1, 3.5 and 4.4 micron) were delivered under the same respiratory regime direct to the RT of 2 Beagle dogs by positive pressure ventilation using a purpose designed administration system. Subsequent to aerosol administration the amount of fluorescein absorbed as a function of time was estimated from plasma concentration versus time and intravenous control data using a modified Loo Riegelman method. Maximum fractional deposition within the RT occurred with 3.5 micron aerosol. Fluorescein was absorbed rapidly from the RT according to an apparent first-order process the rate constant for which was independent of particle size and possibly regional deposition. Average values for absorption half lives in the 2 dogs were 17.3 and 11.4 minutes.

Aerosols↗

PubMed1976

Particle size of dexamethasone incorporated in ointment and its behaviour during penetration in the stratum corneum of living skin.

The particle size of dexamethasone was microscopically determined in polarized light in two emulsion ointments: a standard water-in-old formula (aqueous wool alcohol ointment), and a standard oil-in-water formula (aqueous hydrophilic ointment), both containing 0.023% dexamethasone. The distribution of dexamethasone was on average smaller and finer in the water-in-oil emulsion than in the oil-in-water emulsion. In a further series of experiments we studied by means of the adhesive tape-stripping method the proportions of the particle size and counted the total number of particles in various layers of the stratum corneum in vivo. The difference between the two emulsion types once again proved to be significant, but only as far as the epidermal barrier. A new, uniform particle size spectrum was formed at this level, having a maximum value of 24 mum, which, irrespective of the type of ointment, allows a release of the desamethasone in the live epidermis and dermis. The original particle size distribution is thus qualitatively insignificant in so far as the therapeutic effect of dexamethasone below the barrier zone is concerned. Since the particle size has a strongly distorted frequency distribution, with amarked shift to the left, only about 0.5% of the particles in the w/o emulsion and only about 2% in the o/w emulsion are in fact larger than 56mum, the maximum value measured lying just below the surface of the horny layer. Any loss during further penetration is probably negligible.

Administration, Topical↗

PubMed2003

Low-density-lipoprotein peak particle size in a Mediterranean population.

BACKGROUND: The predominance of small, dense low-density lipoprotein (LDL) particles ('LDL phenotype B') has been associated with a three-fold increased risk of myocardial infarction, but the feasibility of the identification of small, dense LDL as independent predictors of coronary artery disease risk in population studies remains questioned. Design We evaluated the LDL peak particle size and its relation with other established risk factors for coronary heart disease in a group of 156 randomized subjects living on the Mediterranean island of Ustica (71 males and 85 women, range of age 20-69 years), representing approximately 30% of the total population. RESULTS: The prevalence of LDL phenotype B subjects was low (approximately 15% in both men and women) and there was a clear trend for both genders in reducing the LDL peak particle size with age. Moreover, LDL phenotype B subjects had higher BMI values, prevalence of diabetes and plasma triglyceride (TG) levels and lower plasma HDL-C concentrations in comparison with LDL phenotype A individuals; in a multivariate analysis, plasma TG levels were the only variable independently associated with LDL peak particle size. CONCLUSIONS: In this population, which appears to be somewhat protected by premature coronary artery disease, a low prevalence of the LDL pattern B was found in both men and women, and plasma TG could have a key role in regulating the LDL peak particle size. The follow up, still ongoing, will provide useful information on the predictive role of LDL peak particle size on cardiovascular risk, at least in a low-risk population.

Adult↗

PubMedDate not supplied

Particle size reduction of emulsions by formulation design. I: Effect of polyhydroxy alcohols.

The objective of this study was to characterize the effect on particle size and stability of oil-in-water emulsion formulations caused by the addition of polyhydroxy alcohols. Stable soybean oil and hexadecane emulsions were prepared containing increasing amounts of propylene glycol (PG) and glycerol (GLY). A nonionic emulsifier system consisting of Tween 80 and Span 80 was used to achieve optimal stability. Particle size was found to decrease as the level of PG or GLY increased. A three-fold particle size reduction was obtained at a PG level of 40% w/w and at a GLY level of 70% w/w. The particle size of soybean oil emulsions decreased from about 4.8 microns to about 1.7 microns. The particle size of hexadecane emulsions decreased from about 2.7 microns to less than 1 micron. The increase in emulsion viscosity was found to be proportional to the amount of polyhydroxy alcohols added to the formulation. The particle size and creaming stability of the emulsions were found to improve with increasing PG or GLY concentration.

Alkanes↗

PubMed2002

A study of the evolution of the particle boundary layer in a reservoir, using laser particle sizing.

The dynamics of the particle boundary layer in the Boadella reservoir was studied using an in situ laser optical particle-sizing instrument. This layer was found at the bottom of the reservoir from summer until the end of the year, when the reservoir was fully mixed. Most of the particles in this layer are remnants of the summer algae bloom and are trapped in the boundary layer due to the thermal stratification. The phytoplankton bloom is mainly composed of diatoms, with diameter d approximately 5 microm and green algae with diameter d approximately 15 microm. Inorganic particles and decomposed organic particles with d < 3 microm are also encountered in the boundary layer. On the other hand, particles with diameter between 30 and 100 microm are mostly found in the epilimnion of the reservoir. These are a mixture of aggregates of inorganic particles, colonies of phytoplankton, zooplankton, detritus, etc. Different mixing events occurring during autumn resuspended the small particles in the boundary layer, while the greater particles settled down. The extent of the resuspension has been parameterized with a non-dimensional number that balances the stress across the interface and the strength of the stratification.

Diatoms↗

PubMed1997

[Usefulness of particle size distribution analyzer for counting the number of sperm].

We tried to use particle size distribution analyzer to count the number of sperm. The epididymis was removed from male Syrian golden hamsters intratracheally instilled with indium arsenide, indium phosphide or phosphate buffer only, and the homogenate of the cauda epididymidis was used as the sperm sample. The number of sperm counted with particle size distribution analyzer correlated well with the number of sperm counted with hemocytometer (r = 0.96) and the coefficient of the regression line was almost 1. When the same sperm sample was counted repetitively (n = 4), there was no difference in the coefficient of variation between the sperm number counted with particle size distribution analyzer and the sperm number counted with hemocytometer (6.4 +/- 5.8% vs. 7.8 +/- 4.0%). From these results, particle size distribution analyzer was thought to be useful for counting the number of sperm.

Animals↗

PubMed1991

Abnormal particle size of lipoprotein in non-insulin-dependent diabetics and nondiabetics with and without hyperlipidemia.

To clarify the mechanism of the high incidence of ischemic heart disease in the diabetics, we studied the particle size of the lipoprotein with particular attention to the structural abnormality. Using high performance liquid chromatography, the particle size of the lipoprotein was determined with elution volume, which was precisely correlated with the particle size. The particle size of low density lipoprotein (LDL) from the diabetics with normolipidemia is larger than that from the nondiabetics (p less than 0.001) in the elution pattern of triglyceride. The examination of the elution pattern of the triglyceride and cholesterol revealed that this large LDL was composed of a large amount of triglyceride. These characteristics of the large LDL resembled that of the atherogenic intermediate density lipoprotein. The particle size of high density lipoprotein (HDL) from the diabetics with normolipidemia was larger than that from the nondiabetic controls (p less than 0.001), detected by the elution pattern of triglyceride. The comparison of the triglyceride and cholesterol elution pattern indicated that also the large HDL in the diabetics with normolipidemia was rich with triglyceride, which was reported to inhibit the activity of the lipid transfer protein. These facts revealed that the disorder of the lipid metabolism not accompanied with hyperlipidemia produced the large LDL and HDL, which might lead to the excess mortality rate of the ischemic heart disease in the diabetics even with normolipidemia.

Chromatography, High Pressure Liquid↗

PubMed2004

Effects of weight loss on PLTP activity and HDL particle size.

OBJECTIVE: Dyslipidaemia in obesity is characterized by hypertriglyceridaemia, low HDL-C levels, small, dense HDL particles and increased phospholipid transfer protein (PLTP) activity. METHODS: In the present study, we investigated PLTP activity and HDL particle size in 16 morbidly obese, middle-aged women, who underwent Swedish Adjustable Gastric Banding surgery. Study subjects were tested within 2 months before and 1 y after surgery. PLTP activity was determined by exogenous substrate assay and HDL particle size by gradient gel electrophoresis, respectively. RESULTS: Pronounced weight loss after gastric banding surgery resulted in a significant decrease of PLTP activity from 8.42+/-2.04 to 7.43+/-2.21 micromol/ml/h (P=0.02). The size of HDL(2) particles increased signficantly from 14.04+/-0.86 to 14.28+/-0.64 nm (P=0.02) after body weight reduction, while no change in HDL(3) particle size was apparent. DISCUSSION: Our results suggest that dyslipidaemia in obesity is--at least partially--reversible by weight loss. We hypothesize that reduction of PLTP activity and increase of HDL particle size are important component factors in converting the atherogenic lipoprotein profile of obese subjects into a less atherogenic profile with weight loss.

Adult↗

PubMed2002

Separation and characterization of sub-microm- and microm-sized particles by capillary zone electrophoresis.

The analytical separation and characterization of particles in the size range of sub-microm and microm diameters by capillary zone electrophoresis (CZE) has been reviewed. The theoretical basis, on which the mobility can be interpreted to provide information regarding characteristics of particle surface, has shortly been presented. Particular emphasis was put on the model dependence of that interpretation and the need in most applications to forego the classical idealized model of spherical particles with "smooth" surfaces and to apply more realistic models, which take the "hairy" surface of real particles into account. Some highlights of the literature on the CZE of polystyrene latex microspheres, organic and inorganic colloids, lipoprotein particles, viruses, liposomes, biological membrane vesicles, and biological cells have been discussed. Also summarized are the reports on the particle size dependence of mobility and peak broadening in CZE and on electrophoretic behavior of rodlike particles and particle aggregates. Finally, the effects of neutral polymers in the background electrolyte on particle mobility and peak width are reviewed.

Colloids↗

PubMed2002

Relationship between drug effects and particle size of insulin-loaded bioadhesive microspheres.

AIM: To formulate and characterize insulin-loaded adhesive microspheres (MP) and evaluate drug effects of MP with various sizes, 120, 350, and 1000 nm in diameter, in the alloxan-induced diabetic rats. METHODS: Insulin-loaded MP were formulated by an ionotropic gelation procedure. Particle size distributions were determined by photon correlation spectroscopy and optical microscopy. The factors that influenced the particle sizes and loading capacity were investigated, and the release properties were assessed in vitro. The hypoglycemic effect was investigated by monitoring the plasma glucose level of the alloxan-induced diabetic rats after oral administration. RESULTS: All the MPs with three sizes formulated were in the desired size range, and the loading capacity was 15.3 %+/-1.7 % (120 nm), 32.4 %+/-2.4 % (350 nm), and 53.3 %+/-2.7 % (1000 nm) respectively. The particle size also had an influence on the release property of the MPs. Half an hour later, 25 %+/-4 % (120 nm), 18.3 %+/-2.4 % (350 nm), and 8.6 %+/-1.3 % (1000 nm) of insulin were released. MP with different sizes had various degree of hypoglycemic effects after 10 h (P<0.05 vs control insulin solution). The plasma glucose level of 350 nm size particles remarkably decreased 15 h later (P<0.05 vs 120 nm) or 35 h later (P<0.01 vs others). The relative pharmacological availability was 10.2 %+/-0.5 % (120 nm), 14.9 %+/-1.3 % (350 nm), and 7.3 %+/-0.8 % (1000 nm) respectively. Particles of 350 nm showed a comparatively higher availability (P<0.05). CONCLUSION: Adhesive CS-MP were helpful in increasing the relative pharmacological bioavailability of insulin, and a distinct advantage of proper particle size helped to increase the drug effects.

Animals↗

PubMed2006

Metals leachability from medical waste incinerator fly ash: A case study on particle size comparison.

This paper presents the results from a study of metals leachability of medical waste incinerator fly ash in Japan on the basis of particle size. Sequential extraction and Toxicity Characteristic Leaching Procedure (TCLP) analysis were carried out in order to quantify the leaching amount of metals in each categorized particle size. Sequential extraction was also subjected to identify the preference of binding matrix of metals. The results of sequential extraction showed an increase both exchangeable and carbonate associated chromium concentrations in the bigger particle size fractions. Likewise, concentrations of carbonate matrix of arsenic and tin tended to increase in the bigger particle size fractions. In contrast, exchangeable associated cadmium as well as both exchangeable and carbonate matrices of barium were found higher in the smaller particle size fractions. However, no correlation was found in Kendal-tau correlation analysis between particle size of the ash and metals leachability of the TCLP.

Barium↗

PubMed2001

A prospective, population-based study of low density lipoprotein particle size as a risk factor for ischemic heart disease in men.

BACKGROUND: The current interpretation of the increased risk of ischemic heart disease (IHD) associated with reduced low density lipoprotein (LDL) particle size is based entirely on data derived from relatively small case-control studies, with a lack of evidence from large, prospective, population-based cohort data. OBJECTIVES: To investigate the association between LDL particle size and incident IHD on the basis of data from the entire population-based, prospective cohort of men from the Quebec Cardiovascular Study. PATIENTS AND METHODS: Analyses were conducted in a cohort of 2057 men who were all initially free of IHD, and who were followed up over a five-year period, during which 108 first IHD events (myocardial infarction, angina or coronary death) were recorded. LDL particle size was measured by nondenaturing gradient gel electrophoresis. RESULTS: Cox proportional hazards analysis indicated that the relationship between LDL particle size and the risk of future IHD events was not linear. Men with an LDL particle size less than 256.0 A had a significant 2.2-fold increase in the five-year rate of IHD (P<0.001) compared with men having an LDL particle size greater than 256.0 A. Multivariate and subgroup analyses indicated that small, dense LDL particles predicted the rate of IHD independent of LDL cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, apolipoprotein B and the total cholesterol to HDL cholesterol ratio. Finally, the magnitude of the increase in IHD risk attributed to lipid risk factors was modulated to a significant extent by variations in LDL particle size. CONCLUSIONS: The present study provides the first large scale, population-based, prospective evidence supporting the hypothesis that small, dense LDL particles may be associated with an increased risk of IHD. The results also suggest that information on LDL diameter may improve the ability to predict IHD risk accurately over traditional lipid variables.

Age Distribution↗

PubMed1978

Variable-cut particle-size classification by opposing jets.

A new technique of aerodynamic particle-size classification has been developed utilizing axisymmetrically-opposed air jets. For a fixed geometry the cut size can be varied from 0.8 to 3.6 micrometer by changing the jet flow rates. Future designs are expected to extend the useful particle-size range. Particles remain airborne after size separation, permitting the use of continuous, automated methods for analyzing the particle concentration and chemical compositon.

Air Pollutants↗

PubMed2005

Effect of particle size of nanospheres and microspheres on the cellular-association and cytotoxicity of paclitaxel in 4T1 cells.

PURPOSE: To compare the effect of size of delivery systems on the cell-association and in vitro cytotoxicity of paclitaxel. METHODS: Four sizes of PLGA-paclitaxel particles were prepared to study the effect of particle size on the cell-association of paclitaxel in 4T1 monolayer in the presence, and absence, of BCRP inhibitor, endocytic inhibitor, and P-glycoprotein (P-gp) inhibitor. Paclitaxel cell-association studies were repeated in Caco-2, Cor-L23/R, and bovine brain microvessel endothelial cells (BBMECs), as well as the association of etoposide in 4T1 cells. Cytotoxicity of paclitaxel to 4T1 cells delivered in nanospheres was compared to microspheres. RESULTS: The concentration of paclitaxel and etoposide associated with 4T1 cells was 4.8 and 29 times greater, respectively, as the size increased from 310 to 2077 nm. Paclitaxel association consistently increased in Caco-2 and Cor-L23/R as the size of the delivery system increased. The endocytic inhibitor, 2-deoxyglucose, significantly decreased the cellular paclitaxel association when delivered by nanospheres but not microspheres. Consistent with the cell-association results, paclitaxel was thrice more cytotoxic to 4T1 cells when delivered in microspheres. CONCLUSIONS: Cell-association of paclitaxel increased in 4T1, Caco-2, and Cor-L23/R as particle size increased. Paclitaxel delivered from 1-mum microspheres was thrice more cytotoxic to 4T1 cells compared to the drug delivered from nanospheres or solution.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2006

Particle size control in dendrimer-derived supported ruthenium catalysts.

A high-resolution transmission electron microscopy (HRTEM) investigation of a family of supported Ru catalysts prepared from Ru hydroxyl-terminated poly(amidoamine) dendrimer-metal nanocomposite (DMN) precursors has been conducted. Ru particle sizes observed following deposition of DMNs on a HRTEM grid can be controlled within a 0.9-1.4 nm range depending on the metal-to-dendrimer molar ratio. The average particle size in this case correlates well with the theoretically predicted particle size from the molar loading of Ru in the dendrimer. Upon impregnation of Ru-DMNs on Al(2)O(3) and subsequent thermal removal of the dendrimer via reduction at 300 degrees C, significant sintering of the Ru particles was observed. Nevertheless, the resulting supported Ru particles maintained a narrow particle size distribution and average particle size below 2.5 nm. These particle sizes no longer correlate with the metal-to-dendrimer molar ratio but do correlate with the metal-to-dendrimer weight ratio, suggesting that the dendrimer may be acting as a "sintering-control" agent on the catalyst surface. This process is not affected by the surface area of the support, since almost identical particle size distributions were obtained on three different commercial supports.

Journal Article↗

PubMed2004

Optimal particle size of radiocolloid for sentinel node identification in breast cancer-electron microscopic study and clinical comparison.

BACKGROUND: Sentinel node (SN) biopsy using a radiotracer is easy to learn, reproducible, and performed by the majority of breast cancer surgeons. However, this technique raises the question: what is the optimal particle size of colloid? METHODS: Patients were injected with conventional tin colloid (median particle diameter: 700 nm) and the predominant particle size of radiocolloid retained in the SN was measured using electron microscopy. This showed a narrow distribution of colloidal size (100-150 nm). Patients were then injected with modified tin colloid having a median particle size of 100 nm. A clinical comparison was performed between conventional particle size or reduced particle size tin colloid and the SN biopsy success rate, the number of SNs, and the colloidal uptake in SNs. RESULTS: A total of 118 patients were injected with the conventional tin colloid (group I) and 124 patients with the smaller particle colloid (group II). The identification rate and the number of SN in both groups were almost equal, and the patients with low-uptake SNs were not significantly less in group I(p = 0.55). However, in the subgroup of patients 60 years of age or more, group II had significantly more SNs than group I(1.4 vs 1.9; p = 0.03) and low-uptake SNs were significantly less common than in group I(p = 0.02). CONCLUSIONS: The improvement of colloidal uptake in SNs using the smaller particle size tin colloid was confirmed, and this impact was statistically significant in the older population.

Adult↗

PubMed1985

Effects of roughage particle size on site of nutrient digestion and digesta flow through the gastrointestinal tract of sheep fed corncob-concentrate diets.

An experiment examining nutritional effects of dietary corncob particle size was conducted using ruminal-, duodenal- and ileal-cannulated sheep in a 4 X 4 Latin square design. Site of nutrient digestion and digesta flow were the principal criteria evaluated. Analyses of dry matter (DM), N, starch and neutral detergent fiber (NDF) were performed on feed, feces and digesta samples. Chromic oxide-impregnated paper was used as an external marker to estimate digestibilities at different sites along the gastrointestinal tract. Ruminal pH and volatile fatty acid molar proportions were also determined. All diets (74.9% concentrates: 25.1% corncobs) were pelleted and were similar in ingredient composition but varied in corncob particle size (corncob mean particle sizes were 6.5, 5.4, 1.4 or .8 mm). Dietary crude protein levels differed little among treatments. Starch concentration was higher in diets containing the larger corncob particles while NDF, acid detergent fiber (ADF), cellulose and hemicellulose concentrations were lower in diets containing larger particles, suggesting a reaction between starch and fiber moieties during the pelleting process. Starch flow past the duodenum decreased (P less than .05) as dietary corncob particle size decreased. Apparent NDF digestion before the duodenum was highest for sheep fed diets containing 1.4-mm corncobs (P less than .05). Apparent starch digestion in the small intestine decreased (P less than .05) as dietary corncob particle size decreased. A considerable amount of NDF was apparently digested in the small intestine of sheep consuming diets containing 5.4- and .8-mm corncobs. Likewise, a substantial amount of NDF was apparently digested in the large intestine. Few differences in apparent total tract digestibilities were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗