Surfactant coated aerosol powders and their properties

The hygroscopic growth of aerosols is an important factor effecting particle size. The consequence of the hygroscopic growth of pharrnaceutical aerosols is a change in their deposition characteristics, such that there is an increase in the total amount deposited in the lung. In this study the hygroscopic growth of disodium fluorescein (DF) aerosol powders was investigated by coating the powders with lauric and capric acids. The coating procedure was carried out in dichloromethane and chloroform, which acted as cosolvents for the fatty acids. An assessment of the extent and the nature of the coating was carried out. The qualitative assessment of the coating was achieved by infra-red spectroscopy, electronscanning chemical analysis and scanning electron microscopy. The quantitative analysis was carried out by differential refractometry, ultra-violet spectroscopy and gas liquid chromatography. These powders were generated under conditions approaching those in the lung, of 97 % relative humidity and 37"C. Coated and uncoated DF aerosol powders were introduced into a controlled temperature and relative humidity apparatus, designed and constructed for the investigation of hygroscopic growth in these studies. A vertical spinning disc device was used to generate the powders. Under conditions of controlled temperature and relative humidity mentioned, the growth ratio of disodium fluorescein alone was 1.45 compared with 1.68, for a nominal coating of DF with lauric acid of 0.12 gg-1, 1.0 for a nominal lauric acid coating of 0.2 gg-1, and 1.02 for a nominal capric acid coating of 0.18 gg-1. The range of control of hygroscopic growth of these aerosols has implications for the deposition of these preparations in the respiratory tract. These implications are discussed in the light of the current knowledge of the effects of hygroscopic growth on the deposition of pharmaceutical and environmental aerosols. A series of experiments in which pulmonary ventilation using a simple radioaerosol generator and delivery system are reported showing that particle size determination may be used to aid the design of diagnostic aerosol generators

Effect of chloroquine on phagolysosomal fusion in cultured guinea pig alveolar macrophages: Implications in drug delivery

The aim of this study was to evaluate the effects of chloroquine on phagolysosomal fusion (PLF) in cultured guinea pig alveolar macrophages (AMs). This technique may be of significance for antitubercular drugs, because the survival of Mycobacterium tuberculosis is linked to evasion of PLF. Guinea pig AMs were obtained from anesthetized animals after exsanguination. The AMs were cultured at a density of 1×106 cell/mL in 24-well plates after attachment to 13-mm coverslips. Culture conditions were at 37°C, with 95% air/5% CO2 in Roswell Park Memorial Institute (RPMI) 1640 medium with 10% heat-inactivated fetal bovine serum. Rhodamine-dextran (70 kd) was incubated with the cells at 0.25 mg/mL for 24 hours to label the lysosomes. Chloroquine treatment where indicated was performed at 10–20 μ g/mL for 1 hour. Fluorescent BioParticles were then added, and PLF was monitored by formation of an organge-yellow fluorescence on fusion of green fluorescent BioParticles with rhodamine-labeled lysosomes. PLF endpoints were measured by scoring for the percentage of orange-yellow cells in the field of view. Image analysis to measure the intensity of the orange-yellow color was performed by obtaining a, b values for 5×5 pixel areas using the Photo Adobe program 4.0.1

The 2009 Samoa and 2010 Chile Tsunamis as Observed in the Ionosphere using GPS Total Electron Content

Ground‐based Global Positioning System (GPS) measurements of ionospheric total electron content (TEC) show variations consistent with atmospheric internal gravity waves caused by ocean tsunamis following two recent seismic events: the Samoa earthquake of 29 September 2009 and the Chile earthquake of 27 February 2010. Both earthquakes produced ocean tsunamis that were destructive to coastal communities near the epicenters, and both were observed in tidal gauge and buoy measurements throughout the Pacific Ocean. We observe fluctuations in TEC correlated in time, space, and wave properties with these tsunamis using the Jet Propulsion Laboratory’s Global Ionospheric Mapping software. These TEC measurements were band‐pass filtered to remove ionospheric TEC variations with wavelengths and periods outside the typical range for tsunamis. Observable variations in TEC appear correlated with the tsunamis in some locations (Hawaii and Japan), but not in others (Southern California or near the epicenters). Where variations are observed, the typical amplitude tends to be ∼0.1–0.2 TEC units for these events, on the order of ∼1% of the background TEC value. These observations are compared to estimates of expected tsunami‐driven TEC variations produced by Embry Riddle Aeronautical University’s Spectral Full Wave Model, an atmosphere‐ionosphere coupled model, and are found to be in good agreement. Significant TEC variations are not always seen when a tsunami is present, but in these two events the regions where a strong ocean tsunami was observed coincided with clear TEC observations, while a lack of clear TEC observations coincided with smaller sea surface height amplitudes. There exists the potential to apply these detection techniques to real‐time GPS TEC data, providing estimates of tsunami speed and amplitude that may be useful for early warning systems

Novel dry powder preparations of whole inactivated influenza virus for nasal vaccination

The purpose of these studies was to enhance mucosal and systemic antibody production in response to increased local residence time of a whole inactivated influenza virus administered as a dry powder nasal vaccine formulation. Spray-freeze-drying (SFD) particles suitable for nasal delivery were characterized for physico-chemical properties and stability. Mucoadhesive compounds (MA) were characterized for their effects on nasal residence time of vaccine powders in rats compared with published in vitro data and elicited immune responses. SFD particles (D50=26.9µm) were spherical with a specific surface area of 1.25 m2/g. Thermal analysis indicated SFD powders were amorphous and demonstrated improved stability with respect to liquid formulations under various storage conditions. In vitro physico-chemical studies and in vivo scintigraphic imaging experiments indicated sodium alginate (SA) and carboxymethylcellulose-high molecular weight (CMC-HMW) powder formulations most significantly increased residence time in Brown Norway rats. Intramuscular delivery provided equivalent serum antibody titers to intranasal (IN) powder without MA, in the presence of CMC-HMW, SA, and hydroxypropyl methylcellulose (HPMC-HMW) after initial dosing and all formulations except IN powder with chitosan after boosting. IN liquid provided equivalent serum antibody titers to all IN powders after the initial vaccination and significantly greater serum antibody titers than IN powder with chitosan after boosting. Trends were consistent between residence time studies and immune response; however, no statistically significant differences between powder and liquid formulations were observed. It was concluded that enhanced serum and mucosal antibody responses were elicited by a dry powder nasal vaccine, specifically, administered in the presence of sodium alginate

The Guinea Pig as a Model of Infectious Diseases

The words ‘guinea pig’ are synonymous with scientific experimentation, but much less is known about this species than many other laboratory animals. This animal model has been used for approximately 200 y and was the first to be used in the study of infectious diseases such as tuberculosis and diphtheria. Today the guinea pig is used as a model for a number of infectious bacterial diseases, including pulmonary, sexually transmitted, ocular and aural, gastrointestinal, and other infections that threaten the lives of humans. Most studies on the immune response to these diseases, with potential therapies and vaccines, have been conducted in animal models (for example, mouse) that may have less similarity to humans because of the large number of immunologic reagents available for these other species. This review presents some of the diseases for which the guinea pig is regarded as the premier model to study infections because of its similarity to humans with regard to symptoms and immune response. Furthermore, for diseases in which guinea pigs share parallel pathogenesis of disease with humans, they are potentially the best animal model for designing treatments and vaccines. Future studies of immune regulation of these diseases, novel therapies, and preventative measures require the development of new immunologic reagents designed specifically for the guinea pig

Ionospheric Signatures of Tohoku-Oki Tsunami of March 11, 2011: Model Comparisons Near the Epicenter

We observe ionospheric perturbations caused by the Tohoku earthquake and tsunami of March 11, 2011. Perturbations near the epicenter were found in measurements of ionospheric total electron content (TEC) from 1198 GPS receivers in the Japanese GEONET network. For the first time for this event, we compare these observations with the estimated magnitude and speed of a tsunami-driven atmospheric gravity wave, using an atmosphere-ionosphere-coupling model and a tsunami model of sea-surface height, respectively. Traveling ionospheric disturbances (TIDs) were observed moving away from the epicenter at approximate speeds of 3400 m/s, 1000 m/s and 200–300 m/s, consistent with Rayleigh waves, acoustic waves, and gravity waves, respectively. We focus our analysis on gravity waves moving south and east of the epicenter, since tsunamis propagating in the deep ocean have been shown to produce gravity waves detectable in ionospheric TEC in the past. Observed southeastward gravity wave perturbations, seen 60 min after the earthquake, are mostly between 0.5 to 1.5 TECU, representing up to 5% of the background vertical TEC (VTEC). Comparisons of observed TID gravity waves with the modeled tsunami speed in the ocean and the predicted VTEC perturbation amplitudes from an atmosphere-ionosphere-coupling model show the measurements and models to be in close agreement. Due to the dense GPS network and high earthquake magnitude, these are the clearest observations to date of the effect of a major earthquake and tsunami on the ionosphere near the epicenter. Such observations from a future real-time GPS receiver network could be used to validate tsunami models, confirm the existence of a tsunami, or track its motion where in situ buoy data is not available

Phase I, single-dose, dose-escalating study of inhaled dry powder capreomycin : a new approach to therapy of drug-resistant tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) threatens global TB control. The lengthy treatment includes one of the injectable drugs kanamycin, amikacin, and capreomycin, usually for the first 6 months. These drugs have potentially serious toxicities, and when given as intramuscular injections, dosing can be painful. Advances in particulate drug delivery have led to the formulation of capreomycin as the first antituberculosis drug available as a microparticle dry powder for inhalation and clinical study. Delivery by aerosol may result in successful treatment with lower doses. Here we report a phase I, single-dose, dose-escalating study aimed at demonstrating safety and tolerability in healthy subjects and measuring pharmacokinetic (PK) parameters. Twenty healthy adults (n = 5 per group) were recruited to self-administer a single dose of inhaled dry powder capreomycin (25-mg, 75-mg, 150-mg, or 300-mg nominal dose) using a simple, handheld delivery device. Inhalations were well tolerated by all subjects. The most common adverse event was mild to moderate transient cough, in five subjects. There were no changes in lung function, audiometry, or laboratory parameters. Capreomycin was rapidly absorbed after inhalation. Systemic concentrations were detected in each dose group within 20 min. Peak and mean plasma concentrations of capreomycin were dose proportional. Serum concentrations exceeded 2 μg/ml (MIC for Mycobacterium tuberculosis) following the highest dose; the half-life (t1/2) was 4.8 ± 1.0 h. A novel inhaled microparticle dry powder formulation of capreomycin was well tolerated. A single 300-mg dose rapidly achieved serum drug concentrations above the MIC for Mycobacterium tuberculosis, suggesting the potential of inhaled therapy as part of an MDR-TB treatment regimen.Gates Foundation.http://aac.asm.orghb2013ay201