Projected Area Diameter Research Articles

Efficacy of Combined Rifampicin Formulations Delivered by the Pulmonary Route to Treat Tuberculosis in the Guinea Pig Model.

Liposomes, as vehicles alone or in combination with rifampicin (RIF) microparticles (RMs), were evaluated as vehicles to enhance the permeation of RIF into granulomas. RIF liposomes (RLs) were extruded through a 0.1 µm polypropylene membrane. RMs were prepared by the solvent evaporation method. Four weeks after infection, guinea pigs (GPs) were assigned to groups treated with a combination of RM-RLs or RLs alone. RLs were nebulized after extrusion whereas RMs were suspended in saline and nebulized to GPs in a nose-only inhalation chamber. Necropsy was performed after the treatment; the lungs and spleen were resected for bacteriology. RLs had mean diameters of 137.1 ± 33.7 nm whereas RMs had a projected area diameter of 2.48 µm. The volume diameter of RMs was 64 ± 1 µm, indicating that RMs were aggregated. The treatment of TB-infected GPs with RLs significantly reduced their lung bacterial burden and wet spleen weight compared with those treated with blank liposomes. The treatment of TB-infected animals with RM-RLs also reduced their lung bacterial burden and wet spleen weight even though these reductions were not statistically different. Based on these results, the permeation of RIF into granulomas appears to be enhanced when encapsulated into liposomes delivered by the pulmonary route.

Determination of Intrinsic Drug Dissolution and Solute Effective Transport Rate during Laminar Fluid Flow at Different Velocities.

The objective of this study was to determine the intrinsic drug dissolution rate (IDR) and the solute effective transport rate of some drugs, using a single particle dissolution technique, satisfying qualified dissolution conditions. The IDR of three poorly water-soluble compounds was measured in milli-Q water using four different fluid velocities. The enveloped surface area of the particles was calculated from the projected area and the perimeter of the particle observed in the microscope. Furthermore, computational fluid dynamics (CFD) simulations were used to theoretically investigate the flow conditions and dissolution rate, comparing box shaped particles and spherical particles with similar dimensions and surface area as the particles used the experiments. In this study, the IDR measurement of the single particles was determined within 5–60 min using particles with an initial projected area diameter () between 37.5–104.6 µm. The micropipette-assisted microscopy technique showed a good reproducibility between individual measurements, and the CFD simulations indicated a laminar flow around the particles at all flow velocities, even though there were evident differences in local particle dissolution rates. In conclusion, the IDR and solute effective transport rate were determined under well-defined fluid flow conditions. This type of approach can be used as a complementary approach to traditional dissolution studies to gain in-depth insights into the dissolution process of drug particles.

Characterization of ultrafine particles emitted during laser-based additive manufacturing of metal parts

Particulate matter (PM) emitted during laser additive manufacturing with stainless steel powder materials has been studied in detail. Three different additive manufacturing techniques were studied: selective laser melting, direct metal deposition and laser cladding. Gas flow and temperature fields accompanying the processes were numerically modeled for understanding particle growth and oxidation. Transmission and scanning electron microscopy were used for primary particle and PM characterization. The PM collected in the atmosphere during manufacturing consisted of complex aggregates/agglomerates with fractal-like geometries. The overwhelming number of particles formed in the three processes had equivalent projected area diameters within the 4–16 nm size range, with median sizes of 8.0, 9.4 and 11.2 nm. The primary particles were spherical in shape and consisted of oxides of the main steel alloying elements. Larger primary particles (> 30 nm) were not fully oxidized, but where characterized by a metallic core and an oxidic surface shell.

A new method for measuring nanoparticle diameter from a set of SEM images using a remarkable point

Scanning Electron Microscopy (SEM) is considered as a reference technique for the determination of nanoparticle (NP) dimensional properties. Nevertheless, the image analysis is a critical step of SEM measuring process and the initial segmentation phase consisting in determining the contour of each nano-object to be measured must be correctly carried out in order to identify all pixels belonging to it. Several techniques can be applied to extract NP from SEM images and evaluate their diameter like thresholding or watershed. However, due to the lack of reference nanomaterials, few papers deals with the uncertainty associated with these segmentation methods. This article proposes a novel approach to extract the NP boundaries from SEM images using a remarkable point. The method is based on the observation that, by varying the electron beam size, the secondary electron profiles crosses each other at this point. First, a theoretical study has been performed using Monte Carlo simulation on silica NP to evaluate the robustness of the method compared with more conventional segmentation techniques (Active Contour or binarization at Full Width at Half-Maximum, FWHM). The simulation results show especially a systematic discrepancy between the NP real size and the measurements performed with both conventional methods. Moreover, generated errors are NP size-dependent. By contrast, it has been demonstrated that a very good agreement between measured and simulated diameters has been obtained with this new technique. As an example, this method of the remarkable point has been applied on SEM images of silica particles. The quality of the segmentation has been shown on silica reference nanoparticles by measuring the modal equivalent projected area diameter and comparing with calibration certificate. The results show that the NP contour can be very accurately delimited with using this point. The measurement uncertainty has been also reduced from 4.3 nm (k = 2) with conventional methods to 2.6 nm (k = 2) using the remarkable point.

Jamming during particle spreading in additive manufacturing

Additive manufacturing (AM) is going through an exponential growth, due to its enormous potential for rapid manufacturing of complex shapes. One of the manufacturing methods is based on powder processing, but its major bottleneck is associated with powder spreading, as mechanical arching adversely affects both product quality and speed of production. Here we analyse transient jamming of gas-atomised metal powders during spreading. These particles are highly frictional, as they have asperities and multiple spheres and are prone to jamming in narrow gaps. Therefore their detailed characterisations of mechanical properties are critical to be able to reliably predict the jamming frequency as influenced by powder properties and process conditions. Special methods have been used to determine the physical and mechanical properties of gas-atomised stainless steel powders. These properties are then used in numerical simulations of powder spreading by the Discrete Element Method. Particle shape is reconstructed for the simulations as a function of particle size. The characteristic size D90 by number (i.e. the particle size, based on the projected-area diameter, for which 90% of particles by number are smaller than this value) is used as the particle dimension accountable for jamming. Jamming is manifested by empty patches over the work surface. Its frequency and period have been characterised as a function of the spreader gap height, expressed as multiple of D90. The probability of formation of empty patches and their mean length, the latter indicating jamming duration, increase sharply with the decrease of the gap height. The collapse of the mechanical arches leads to particle bursts after the blade. The frequency of jamming for a given survival time decreases exponentially as the survival time increases.

Contributions of transported Prudhoe Bay oil field emissions to the aerosol population in Utqiaġvik, Alaska

Abstract. Loss of sea ice is opening the Arctic to increasing development involving oil and gas extraction and shipping. Given the significant impacts of absorbing aerosol and secondary aerosol precursors emitted within the rapidly warming Arctic region, it is necessary to characterize local anthropogenic aerosol sources and compare to natural conditions. From August to September 2015 in Utqiaġvik (Barrow), AK, the chemical composition of individual atmospheric particles was measured by computer-controlled scanning electron microscopy with energy-dispersive X-ray spectroscopy (0.13–4 µm projected area diameter) and real-time single-particle mass spectrometry (0.2–1.5 µm vacuum aerodynamic diameter). During periods influenced by the Arctic Ocean (70 % of the study), our results show that fresh sea spray aerosol contributed ∼ 20 %, by number, of particles between 0.13 and 0.4 µm, 40–70 % between 0.4 and 1 µm, and 80–100 % between 1 and 4 µm particles. In contrast, for periods influenced by emissions from Prudhoe Bay (10 % of the study), the third largest oil field in North America, there was a strong influence from submicron (0.13–1 µm) combustion-derived particles (20–50 % organic carbon, by number; 5–10 % soot by number). While sea spray aerosol still comprised a large fraction of particles (90 % by number from 1 to 4 µm) detected under Prudhoe Bay influence, these particles were internally mixed with sulfate and nitrate indicative of aging processes during transport. In addition, the overall mode of the particle size number distribution shifted from 76 nm during Arctic Ocean influence to 27 nm during Prudhoe Bay influence, with particle concentrations increasing from 130 to 920 cm−3 due to transported particle emissions from the oil fields. The increased contributions of carbonaceous combustion products and partially aged sea spray aerosol should be considered in future Arctic atmospheric composition and climate simulations.

Spectroscopic Determination of Aerosol pH from Acid-Base Equilibria in Inorganic, Organic, and Mixed Systems.

Atmospheric aerosol acidity impacts key multiphase processes, such as acid-catalyzed reactions leading to secondary organic aerosol formation, which impact climate and human health. However, traditional indirect methods of estimating aerosol pH often disagree with thermodynamic model predictions, resulting in aerosol acidity still being poorly understood in the atmosphere. Herein, a recently developed method coupling Raman microspectroscopy with extended Debye-Hückel activity calculations to directly determine the acidity of individual particles (1-15 μm projected area diameter, average 6 μm) was applied to a range of atmospherically relevant inorganic and organic acid-base equilibria systems (HNO3/NO3-, HC2O4-/C2O42-, CH3COOH/CH3COO-, and HCO3-/CO32-) covering a broad pH range (-1 to 10), as well as an inorganic-organic mixture (sulfate-oxalate). Given the ionic strength of the inorganic solutions, the H+ activity, γ(H+), yielded lower values (0.68-0.75) than the organic and mixed systems (0.72-0.80). A consistent relationship between increasing peak broadness with decreasing pH was observed for acidic species, but not their conjugate bases. Greater insight into spectroscopic responses to acid-base equilibria for more complicated mixtures is still needed to understand the behavior of atmospheric aerosols.

Inhalation of nanoplatelets – Theoretical deposition simulations

Primary objective of the contribution was the theoretical prediction of nanoplatelet deposition in the human respiratory tract. Modeling was founded on the hypothetical inhalation of graphene nanoplatelets (GNP) measuring 0.01 and 0.1μm in thickness and adopting a projected area diameter of 1–30μm. Particle uptake was assumed to take place with inhalation flow rates of 250, 500, 750, and 1000cm3s−1, respectively. For an appropriate description of pulmonary particle behavior, transport of GNP in a stochastic lung structure and deposition formulae based on analytical and numerical studies were presupposed. The results obtained from the theoretical approach clearly demonstrate that GNP with a thickness of 0.01μm deposit in the respiratory tract by 20–50%, whereas GNP with a thickness of 0.1μm exhibit a deposition of 20–90%. Larger platelets deposit with higher probability than small ones. Increase of inhalation flow rate is accompanied by decreased deposition in the case of thin GNP, whilst thicker GNP are preferably accumulated in the extrathoracic region. Generation-specific deposition ranges from 0.05 to 7% (0.01μm) and from 0.05 to 9%, with maximum values being obtained in airway generation 20. In proximal airway generations (0–10), deposition is increased with inhalation flow rate, whereas in intermediate to distal generations a reverse effect may be observed. Health consequences of GNP deposition in different lung compartments are subjected to an intense debate.

Effects of size and shape on filtration of TiO2 nanoparticles

ABSTRACTTitanium dioxide (TiO2) is one of the most widely used nanoscale materials to date and could result in human exposures. The main objective of this study was to perform detailed characterization of TiO2 agglomerate particles and how these properties influence particle penetration in a screen filter. Transmission electron microscope (TEM) photos showed compact agglomerates of nanoscale primary particles. The projected area diameter was close to the mobility diameter, where the length was about 25% larger than the mobility diameter. The mean aspect ratio of TiO2 agglomerate was constant between 1.39 and 1.55. Using the tandem differential mobility analyzer-aerosol particles mass analyzer (DMA-APM) technique, we were able to measure aerodynamic diameter, mass, and fractal dimension. The value of fractal dimension based on mass and mobility diameter was 2.8. Penetration of classified TiO2 particles through a screen filter was measured. Penetration increased with increasing mobility diameter and flow ra...

Contributions of Long-Range Transported and Locally Emitted Nitrate in Size-Segregated Aerosols in Japan at Kyushu and Okinawa

ABSTRACTWe observed the size distributions of mass concentration, ionic composition, and trace metal concentration in aerosols collected at an urban site in Kumamoto Prefecture (KM) and a rural site at Cape Hedo in Okinawa Prefecture (HD) between 2012 and 2015. To evaluate the contribution of transboundary nitrate and locally emitted nitrate in the aerosols at Kumamoto, we distinguished between days of transboundary air pollution from East Asia and days of local air pollution on the basis of a threshold for Pb concentration and the ratio Pb (in 0.5 < projected area diameter (Dp) < 1.0 µm)/Cu (in 2.5 < Dp < 10 µm). Fine nitrate (particulate NH4NO3) did not arrive at HD from the Asian continent even under long-range transport conditions. Fine nitrate emitted in Kumamoto and its vicinity also was not transported to HD, even in an air mass that passed over KM and reached HD within one day. Almost all fine nitrate was converted to coarse nitrate during transport by dissociation of fine nitrate and adsorption of HNO3 on larger aerosol particles. Transboundary nitrate existed largely in the particle size range of 0.5 < Dp < 10 µm, and the contribution of transboundary nitrate in the particle size range of 0.1 < Dp < 0.5 µm was about 20% even under long-range transport conditions. The contribution of transboundary nitrate in particles with Dp < 2.5 µm at KM was approximately 50%, 50%, and 80% in spring, autumn, and winter, respectively.

Behaviour and dynamics of two bubbles in conjunct condition in high‐viscosity liquids

AbstractTwo bubbles in conjunct condition are often encountered in high‐viscosity liquids, but have received very little attention in the literature. The conjunct bubbles rise together with unchanged shapes and constant velocities, showing some unique properties compared to single bubbles. The current research built on the previous work of Cai et al.,[1] and extended the bubble size ratio (κ) to the range 1.0–1.2. The formation and motion characteristics of conjunct bubbles made by direct collision of two in‐line bubbles were investigated, including the effects of bubble volume, bubble size ratio, and liquid viscosity. Models for the conjunct bubbles and the single bubbles were provided for predicting the projected area diameters and the rising velocities respectively, and the predicted values closely agreed with the measurements in glycerol‐water solutions with Morton numbers in the range of 1.690–661.8. The dynamic forces on the conjunct bubbles were analyzed, and a succinct algorithm was proposed for calculating the drag forces on the conjunct bubbles and the interaction force between the two bubbles.

Measurement of transport properties of aerosolized nanomaterials

Airborne engineered nanomaterials such as single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), functionalized MWCNT, graphene, fullerene, silver and gold nanorods were characterized using a tandem system of a differential mobility analyzer and an aerosol particle mass analyzer to obtain their airborne transport properties and understand their relationship to morphological characteristics. These nanomaterials were aerosolized using different generation methods such as electrospray, pneumatic atomization, and dry aerosolization techniques, and their airborne transport properties such as mobility and aerodynamic diameters, mass scaling exponent, dynamic shape factor, and effective density were obtained. Laboratory experiments were conducted to directly measure mobility diameter and mass of the airborne nanomaterials using tandem mobility-mass measurements. Mass scaling exponents, aerodynamic diameters, dynamic shape factors and effective densities of mobility-classified particles were obtained from particle mass and the mobility diameter. Microscopy analysis using Transmission Electron Microscopy (TEM) was performed to obtain morphological descriptors such as envelop diameter, open area, aspect ratio, and projected area diameter. The morphological information from the TEM was compared with measured aerodynamic and mobility diameters of the particles. The results showed that aerodynamic diameter is smaller than mobility diameter below 500nm by a factor of 2–4 for all nanomaterials except silver and gold nanorods. Morphologies of MWCNTs generated by liquid-based method, such as pneumatic atomization, are more compact than those of dry dispersed MWCNTs, indicating that the morphology depends on particle generation method. TEM analysis showed that projected area diameter of MWCNTs appears to be in reasonable agreement with mobility diameter in the size range from 100 to 400nm. Principal component analysis of the obtained airborne particle properties also showed that the mobility diameter-based effective density and aerodynamic diameter are eigenvectors and can be used to represent key transport properties of interest.

A novel image analysis approach for evaluation of mixing uniformity in drug-filled silicone rubber matrix

Nowadays, there is a lot of interest in developing long-acting drug delivery devices for human or veterinary applications including monolithic systems. Drug content uniformity of a monolithic device is highly dependent on the uniform distribution of drug particles within the polymeric matrix both in dispersion and distribution levels. Here, a range of formulations were prepared which consisted of progesterone (1%w/w) and estradiol benzoate (0.1%w/w) dispersed in a silicone rubber matrix. Blend uniformity of the compounds was analyzed by image analysis of SEM micrographs obtained from the cross-sections of the devices by a new image processing approach. Efficiency of mixing was investigated at the dispersion level by plotting the relative frequency of drug particles versus “projected area diameter” of their aggregates. Based on the particle size distribution results, a significant improvement was observed in the dispersion pattern of drug particles by adding silicone oil (9%w/w). Distribution pattern of the particles was investigated by transforming the micrographs into algebraic matrices. An “ideal matrix” was developed by assumption of uniform localization of the drug particles. Real matrices obtained for all of the formulations were compared with this ideal matrix as a reference. Closer similarity between the two matrices was observed for silicone oil-containing (9%w/w) samples showing the best dispersive and distributive mixing quality.

Comparison of Filter and Wall Deposits From Samplers Used to Collect Airborne Lead-Containing Dusts at Field Sites

Pairs of Institute of Occupational Medicine (IOM) and 37 mm closed face cassette samplers (CFC) were deployed where occupational exposures to lead-containing dusts were known to occur. Discrete particle analyses of wall and filter deposits were performed by Scanning Electron Microscopy—Energy Dispersive X-ray Spectrometry (SEM-EDX). From the elemental composition and projected area diameter of each particle a density, volume, and mass were calculated, and a mass-weighted size distribution for each filter and corresponding wall deposit determined. Comparison of pairs of wall and filter mass-weighted size distributions by Mann–Whitney statistical analysis shows that in only 3 of 72 examples from either sampler were the distributions significantly different that suggests that the mechanisms of particle deposition on the sampler walls for particles in this size range (0.5 μm through 20 μm) do not differ for the different samplers. Furthermore, in only 4 of 33 sampler pairs did the IOM and CFC results differ. ...

Granule formation mechanisms and morphology from single drop impact on powder beds

Single drops impacting static powder beds were studied to explain the different resulting granule structures. Three chemically similar powders with different physical properties formed static beds with porosities of 0.66–0.69, 0.54, and 0.30–0.35 respectively. Three different binder fluids (distilled water and silicone oils with viscosities of 9.3 and 96 mPa s) were released onto these powder beds from two different heights (0.5 and 30 cm). The initial drop impact, as well as complete penetration of the droplet into the bed, was recorded with a high speed camera. The high speed camera videos were analyzed, and three different granule formation mechanisms were identified: Tunneling, Spreading, and Crater Formation. Tunneling occurred for loose, cohesive powder beds. Powder aggregates were sucked into the drop which then tunneled into the beds. For coarser powders, granules were formed by a Spreading mechanism at a low impact velocity. At a high impact velocity, the drop formed a crater in the bed surface and deformed elastically in the crater, coating the drop in a layer of powder before penetrating into the bed by capillary action. Using all three dimensions of the granule, a new shape factor, the vertical aspect ratio (the ratio of the granule's projected area diameter to its maximum vertical height), was proposed as a more accurate descriptor of granule shape than currently used descriptors such as the horizontal aspect ratio. The different granule shapes observed were explained by the granule formation mechanisms. The Tunneling mechanism always produced round granules, the Spreading mechanism always produced flat disks, and the Crater Formation mechanism produced granules of varying shapes that were dependant on liquid binder properties. The results of this study have important implications for being able to predict granule structure from granule formation mechanisms, and to be able to choose the desired granule properties by operating in the appropriate regime.

Image Analysis Optimization for Quantifying Nanoparticle Dispersions in Polymer-based Nanocomposites Using Transmission Electron Microscopy (TEM)

ABSTRACTWhen comparing large numbers of TEM micrographs of insoluble additives in polymer-based nanocomposite systems, the ability to determine or estimate the dispersion quality (i.e. uniformity of size and/or spatial distribution) is often difficult. The objective of this study was to develop a method to quantify dispersions observed in TEM micrographs that enables both a numerical “ranking” to be assigned to individual dispersions as well as tabulation a multitude of images acquired over time. Several methods were reviewed and applied to a set of TEM dispersion images of an insoluble additive in polystyrene. Projected area diameter, particle area, and Euclidean distance between particle centroids were chosen from all the particle size distribution and spatial distribution parameters present in the literature, but none successfully yielded a quantitative indicator of dispersion quality for the micrographs. In contrast, generating cumulative volume percent curves for each sample appeared to be a preferred method of quantifying and comparing dispersions in TEM micrographs. The volume diameter values obtained by this method can be used for “ranking” and tabulation of dispersion quality and account for both “good” additive dispersions (i.e. those with small domains of a narrow size range around 1 μm or less) and “bad” additive dispersions (i.e. those with non-uniform domains ranging in size by several microns or more). As a result, the numerical values generated by this method can be used to quantitatively determine correlations between the dispersion quality of nanoparticles in polymer-based nanocomposite materials and various macroscale physical and/or performance properties of such materials. This method’s precision was statistically determined to decrease with increasing particle size and be heavily dependent on representative sampling.

Source analysis of fine and coarse particulate matter from livestock houses

The analyses of the different sources which can contribute to particulate matter (PM) emissions from livestock houses are essential to develop adequate reduction techniques. The aim of this study was to morphologically and chemically characterize several sources of PM from livestock houses. We collected known sources of PM from different housing systems for poultry and pigs, which were later aerosolized in a customized laboratory dust generator to collect fine and coarse PM samples. These samples were morphologically and chemically characterized using scanning electron microscopy with X-ray microanalysis to develop comprehensive morphological and chemical source profiles. Moreover, source particle-size distribution was determined. Results showed distinct and unique particle morphologies in collected sources from different housing systems for poultry and pigs. Although presence of N, Na, Mg, Al, Si, P, S, Cl, K, and Ca were identified in all sources, their relative element concentrations varied amongst sources and could be used to discriminate amongst them. Particle size and size distribution also varied amongst sources (size ranged from 2.1 μm to 18.1 μm projected area diameter), and mainly depended on its mineral or organic origin. The results from this work can be useful information for source identification and quantification in PM from livestock houses, improving the understanding of how PM is generated in such environments, and developing strategies for its reduction.

Characterisation of individual aerosol particles on moss surfaces: implications for source apportionment

The size, morphology and chemical composition of 8405 particles on moss surfaces (Hylocomium splendens) was investigated by scanning electron microscopy and energy-dispersive X-ray microanalysis. Two moss samples from three locations in Southern Norway (Algård, Birkeland, Neslandsvatn) and two sampling years (1977 and 2005) each were selected leading to a total of 12 samples investigated. At all three locations, particle deposition decreased substantially with time. The major particle groups encountered include silicates, iron-rich silicates, metal oxides/hydroxides, iron oxides/hydroxides, carbonates, carbon-rich particles, silicate fly ashes, iron-rich silicate fly ashes, and iron oxide fly ashes. Between 1977 and 2005, the relative number abundance of the three fly ash groups decreased substantially from approximately 30-60% to 10-18% for the small particles (equivalent projected area diameter <1 microm), and from 10-35% to 2-9% for large particles with diameters ≥1 microm. This decrease of fly ash particles with time was overlooked in previous papers on atmospheric input of pollutants into ecosystems in Southern Norway. In general, the presence of fly ash particles is ignored in most source apportionment studies based on bulk chemical analysis. Consequently, the geogenic component (crustal component) derived from principal component analysis is overestimated systematically, as it has a similar chemical composition as the fly ash particles. The high abundance of fly ashes demonstrates the need to complement source apportionment based on bulk chemistry by scanning electron microscopy in order to avoid misclassification of this important anthropogenic aerosol component.

Engineering Data of Diameter Change during Air Drying of Milk Droplets with 40 wt% Initial Solids Content

Spray drying of liquid food droplets is one of the primary means of manufacturing food powders today. Modeling this process requires single-droplet drying modeling, and droplet size change during drying is one part of such modeling. Some experimental data of milk droplet diameter change at 20 and 30 wt% are reported in literature.[ 1 ] Data are not available at higher solid contents, which are of interest to the industry. We now report the experimental results of the effects of drying conditions on milk droplet size change (using projected area diameter as the parameter) using the glass filament technique, complimented by video imaging analysis software. Under the constant drying air conditions for solids content of 40 wt%, and for both skim and whole milk, the droplet diameter changes were correlated using the previous model of Lin and Chen.[ 1 ] With previous data together, the shrinkage coefficients were correlated against solids content.

Screening for Potential Adjuvants Administered by the Pulmonary Route for Tuberculosis Vaccines

Tuberculosis (TB) infects one third of the world's population, and new infections occur at a rate of 1/s. Better vaccines are needed than the live mycobacterium Bacille Calmette-Guérin (BCG). Alveolar macrophages (AMPhis) play a central role in pulmonary manifestations of TB. Targeting immunomodulators to AMPhis, the first line of defense against Mycobacterium tuberculosis (Mtb), may initiate a potent cell-mediated immune response. Muramyl dipeptide (MDP) and trehalose dibehenate (TDB) have elicited strong immune response when delivered to the lungs as aerosols. AMPhis show toxicity in response to some immunomodulators. The objective of this work was to screen the immunomodulators MDP and/or TDB encapsulated in microparticles (MPs) and to evaluate certain indicators of toxicity in human AMPhi-like cells. Poly(lactide-co-glycolide) (PLGA) MPs containing MDP and/or TDB were prepared by spray-drying. The morphology, particle size distribution, and immunomodulator encapsulation efficiency of MPs were examined. THP-1 cells were exposed to these MPs for 24 h and characteristics of cell morphology, tumor necrosis factor-alpha (TNF-alpha) release, lactate dehydrogenase (LDH), N-acetyl-beta-D: -glucosaminidase (NAG) and alkaline phosphatase (ALP) activity in AMPhi culture supernatants were measured. MTT assay was used to assess the viability of cells. Spray-drying produced low-density MPs having volume median diameters between 4 and 6 microm as measured by laser diffraction and projected area diameter between 3 and 5 microm calculated by microscopy. More TNF-alpha was produced by THP-1 cells exposed to MPs composed of PLGA-MDP or PLGA alone than PLGA-TDB. LDH release following exposure to MPs of PLGA-MDP and PLGA alone was greater than controls. NAG release was higher following exposure to MPs of PLGA alone or PLGA-MDP 0.1% than PLGA-TDB (0.1% and 1.0%). Cells remained viable after exposure to MPs as per MTT assay. PLGA-MDP MPs demonstrated statistically elevated indicators of biochemical responses in cell culture compared to PLGA-TDB MPs, but the extent of their potential to elicit adverse effects in vivo must be studied independently.