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PubMed1995

The delivery of aerosolized steroids from MDIs with nozzle extensions: quantitative laboratory evaluation of a method to improve aerosol delivery to intubated patients.

OBJECTIVE: Pulmonary deposition of aerosolized drug from a metered dose inhaler (MDI) is low with intubated patients. In the laboratory, extension of the MDI nozzle to the endotracheal tube tip has been shown to increase the delivered dose of albuterol. The objectives of this study were to determine the dose of aerosolized steroid (beclomethasone and triamcinolone) delivered through a MDI nozzle extension, the effect of nozzle extension length and number of actuations on the delivered dose, and particle size delivered through the nozzle extension. DESIGN: A 19-G catheter was used as the MDI nozzle extension. The nozzle extension was attached to a 60-ml syringe via the Luer-Lok connection, and the distal end was directed through a hole drilled into a 15-ml capped tube. The MDI was placed into the syringe and actuated by pressing the syringe plunger. Drug delivered through the nozzle extension into the tube was dissolved in methanol (beclomethasone) or ethanol (triamcinolone). Nozzle extension lengths of 10 cm, 20 cm and 30 cm were studied. For each nozzle extension length, delivery was assessed using one, two, three and five actuations of each drug. Drug remaining in the nozzle extension was recovered by rinsing with the appropriate solvent. Aerosol particle size leaving the nozzle extension was determined using a seven-stage cascade impactor. Beclomethasone and triamcinolone concentrations were determined by spectrophotometry at 239 nm. SETTING: Respiratory care laboratory of a university teaching hospital. RESULTS: For the pooled results, 70.2 +/- 14.1% of the dose was delivered through the nozzle extension, with no difference between beclomethasone and triamcinolone (p = 0.838). The proportion of drug delivered through the 10-cm extension (76.7 +/- 8.4%) was greater than that from the 20-cm (66.1 +/- 16.5%) and 30-cm (67.7 +/- 13.9%) extensions (p = 0.001). Less drug was delivered through the extension with one actuation (54.1 +/- 17.7%) than with two (71.2 +/- 7.7%), three (77.2 +/- 5.5%), or five actuations (78.2 +/- 4.3%) (p < 0.001). There was a decrease in MMAD with increasing nozzle extension length (3.14 +/- 0.61 microns for 10 cm, 2.97 +/- 0.28 microns for 20 cm, 2.37 +/- 0.27 microns for 30 cm; p = 0.005). CONCLUSIONS: A high proportion of aerosolized steroid was delivered with a MDI actuated through a nozzle extension. The proportion delivered through the nozzle extension was significantly less with longer nozzle extensions and with fewer actuations, but this may not be clinically important. Although particle sizes were smaller from longer nozzle extensions, all were within the respirable range. These results suggest that steroids can be delivered efficiently using a MDI nozzle extension.

Aerosols↗
PubMed1996

Aerosolized specific antibody protects mice from lung injury associated with aerosolized ricin exposure.

Parenteral vaccination with ricin toxoid, although protective against death after a lethal aerosol ricin challenge, only partially protects against lung lesions. Therefore, we tested whether passive protection with aerosolized specific anti-ricin IgG (goat polyclonal, affinity-purified) could protect against both lethality and lung lesions in unvaccinated mice. Healthy CD-l mice were administered antibody (Ab) by small particle aerosol. Group 1 received non-specific control Ab (2160 mg/min/m3), and groups 2 and 3 received anti-ricin IgG (960 and 3280 mg/min/m3, respectively). Each group was challenged with a lethal dose of aerosolized ricin 1 hr after Ab exposure. All group 1 (control Ab) mice developed diffuse airway epithelial necrosis, with severe interstitial edema and inflammation involving all lung lobes, and died 48-96 hr post-challenge (PC). In contrast, in groups 2 and 3 at 24 hr PC, lung lesions were absent to very mild although there was rare epithelial necrosis in the upper airways in both groups. By 48 hr PC, necrosis of the tracheal epithelium and peritracheal inflammation were noted in some group 3 mice only. By 4 days PC, lungs and airways did not differ from cage controls in most group 2 and 3 mice. Weight gain in group 2 and 3 mice paralleled that of control mice. At 14 days PC, lungs were no different in controls than in group 3 mice. However, two non-survivors in group 3 had obstructions due to proximal airway epithelial damage. All group 2 mice survived, although a mild lymphoplasmacytic perivasculitis was present at 14 days PC which was not noted in the group 3 mice.

Administration, Inhalation↗
PubMed1984

Biological availability of lead in a paint aerosol. 1. Physical and chemical characterization of a lead paint aerosol.

This study was conducted to determine the physical and chemical characteristics of an aerosol of lead-based paint, generated in an industrial spray operation, that might influence the biological availability of lead present in inhaled aerosols. Paint aerosols were collected, and mass-size distribution was determined using a portable cascade impactor under actual occupational conditions. Approx. 2% of the particulate mass collected was in the respirable range (less than 10 micron mean aerodynamic diameter), although the maximum airborne concentration of lead was found to be 2-3 mg/m3. The lead concentration in a dried aerosol was very resistant to chemical digestion. Analysis by X-ray diffraction, atomic absorption spectroscopy and inductively coupled plasma emission spectroscopy showed approx. 11% lead by dry weight, although the wet weight concentration of lead reported by the manufacturer was 12.8%.

Aerosols↗
PubMed2001

Formation of aerosol particles from reactions of secondary and tertiary alkylamines: characterization by aerosol time-of-flight mass spectrometry.

In ambient field studies conducted with aerosol time-of-flight mass spectrometry (ATOFMS), individual particle mass spectra commonly contain ion peaks at mass/charge (m/z) 86, 101, 102, and 118. Particles with mass spectra containing these peaks show a strong correlation with high relative humidity and low temperatures. In an effort to identify these peaks, a series of smog chamber studies were conducted probing the chemistry of secondary and tertiary alkylamines. Specifically, in separate studies, trimethylamine, di- and triethylamine, and di- and tripropylamine were reacted in a 1 m3 Teflon outdoor smog chamber with naturally occurring levels of gas phase oxidants in ambient air. The aerodynamic sizes and individual mass spectra of the resulting aerosol particles were acquired continuously using aerosol time-of-flight mass spectrometry (ATOFMS). Both oxidation and acid-base reactions between amines and acids commonly present in the atmosphere (i.e., nitric and sulfuric acid) appear to play roles in the formation and chemistry of organic nitrogen-containing particle phase species. Ion peaks in the individual particle mass spectra indicate the presence of alkyl ammonium salts, as well as other tentatively identified organic N-containing compounds formed by oxidation processes. Also, for the first time, tertiary alkylamine-N-oxides have been identified as alkylamine oxidation products in the aerosol particle phase. Smog chamber reactions involving triethylamine produce ATOFMS mass spectra with similar ion peak combinations as those observed in the spectra of particles commonly detected in ambient and vehicular source characterization studies. The results of this study suggest that amine chemistry involving gas-to-particle conversion and photooxidation processes may play a significant role in particle formation in regions with high amine concentrations.

Aerosols↗
PubMed1997

Aerosol deposition in equine lungs following ultrasonic nebulisation versus jet aerosol delivery system.

Therapeutic aerosols pay an increasing role in the treatment of equine respiratory disorders. This route of delivery permits concentration of significant amounts of drugs at the site of action without unwanted high systemic concentration and resultant side effects. The efficiency of such a topical therapy depends on the quantity of inhaled drugs deposited in the lungs and, for some drugs, on the proportion retained in specific parts of the lungs. The objective of this study was to define and to compare quantitative (dose deposited) and qualitative (regional distribution) deposition of an aerosol in the equine lungs, using either a ultrasonic nebuliser (UN) currently used in human medicine or a high pressure jet nebuliser (JN) especially developed for the equine species. This comparison was possible owing to gamma-scintigraphy, a noninvasive technique ideally suited to give information about both total and regional deposition of inhaled drugs in the respiratory tract. The quantitative study did not point out any difference between the 2 systems concerning the activity released from the nebuliser proportionally to the initial loaded dose (mean +/- s.d. 45.95 +/- 4.93% for the UN vs. 46.47 +/- 8.49% for the JN). By contrast, the percentage of the dose released reaching the lungs was significantly lower with the UN compared to the JN (5.09 +/- 0.66% vs. 7.35 +/- 1.96%). The qualitative analysis did not show any significant difference in size of aerosol deposition image between the 2 nebulisers. However peripheral deposition was significantly higher with JN compared to UN. In conclusion, both nebulisers may be used for aerosol therapy in the equine species. The ultrasonic and pneumatic nebulisation achieved drug deposition in the peripheral part of the lungs (i.e. small airways and lung parenchyma).

Administration, Inhalation↗
PubMed2002

Moving from CFC aerosol to HFA aerosol or dry powder inhalers: what do patients think?

BACKGROUND/OBJECTIVES: Environmentally friendly hydrofluoroalkane (HFA) pressurised metered-dose inhalers are currently being marketed to replace chlorofluorocarbon (CFC)-driven devices. It is uncertain whether these new formulations with different properties are acceptable to patients. Similarly, switching a patient to a dry powder inhaler (DPI) carries the risk of non-acceptance. METHODS: One hundred patients with obstructive airway disease on regular CFC aerosol inhaler medication underwent a standardised, structured interview. During the interview patients were asked to use a new HFA aerosol inhaler and three DPIs in random order. Patients' notions were recorded. RESULTS: Most patients (96) agreed to change from their CFC to the HFA inhaler, of those, only 12 did so with some reservation. Properties (taste, user-friendliness, design) of the HFA inhaler were rated favourably. DPIs represented an acceptable alternative to aerosol inhalers. In fact, 57 patients preferred a DPI over the HFA inhaler. Not all powder devices were equally acceptable. Replacing the CFC inhaler with patients' preferred alternative devices resulted in a more than 3-fold increase in costs. CONCLUSION: Concerns about the acceptability of reformulated CFC-free aerosol inhalers are ill founded. However, if given the choice, many patients prefer a DPI over the HFA inhaler. The transition offers an opportunity to review patients' current treatment and the proficiency of their inhaling technique. Moving to CFC-free inhalers will have revenue implications.

Adolescent↗
PubMed1990

Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patients. Comparison of dose to the lungs.

The purpose of this study was to compare deposition of aerosol to the lung from a metered-dose inhaler (MDI) and aerosol holding chamber and from a jet nebulizer in ventilator-dependent patients. Twenty-one patients were entered into the study, all receiving assisted ventilation and inhaled bronchodilators because of airflow limitation. The average age was 68 yr; there were 10 men and 11 women. The patients were randomized to receive either 4 puffs (800 micrograms) of radiolabeled fenoterol by MDI of 1.75 ml (1,750 micrograms) of radiolabeled fenoterol solution by nebulizer. Imaging of lung fields was made by a portable scintillation camera at 5-min intervals during the study. Results showed that 20 patients completed the study, 9 receiving fenoterol by MDI, and 11 by jet nebulizer. Four were excluded from analysis because of previous pneumonectomy, two from each group. Lung deposition measured as a percent of given dose from either system was 5.65 +/- 1.09 (mean +/- SEM) for MDI plus extension chamber and 1.22 +/- 0.35 for jet nebulizer (p less than 0.001). Therefore, this trial shows significantly greater efficiency of aerosol deposition to the lung in ventilator-dependent patients when using an MDI plus aerosol holding chamber than when using a jet nebulizer.

Aerosols↗
PubMed2004

Development of a size-dependent aerosol deposition model utilising human airway epithelial cells for evaluating aerosol drug delivery.

Aerosol delivery to the airways of the human respiratory tract, followed by absorption, constitutes an alternative route of administration for compounds unsuitable for delivery by conventional oral and parenteral routes. The target for aerosol drug delivery is the airways epithelium, i.e. tracheal, bronchial, bronchiolar and alveolar cells, which become the site of drug deposition. These epithelial layers also serve as a barrier to the penetration of inhaled material. An in vitro model for aerosol deposition and transport across epithelia in the human airways may be a good predictor of in vivo disposition. The present preliminary studies begin an investigation that blends the dynamics of aerosol delivery and the basis of an in vitro simulated lung model to evaluate the transport properties of a series of molecular weight marker compounds across human-derived bronchiolar epithelial cell monolayers. An Andersen viable cascade impactor was used as a delivery apparatus for the deposition of size-segregated particles onto monolayers of small airway epithelial cells and Calu-3 cells. It was shown that these cell layers can withstand placement in the impactor, and that permeability can be tested subsequent to removal from the impactor.

Administration, Inhalation↗
PubMed1989

Altered clearance of inhaled 99mTc-pentetate aerosols following exposure to cadmium chloride aerosols in ferrets.

The rate of clearance of inhaled 99mTc-pentetate aerosols has been used as an indicator of pulmonary epithelial "permeability" in human and animal studies. In order to evaluate this technique further, groups of eight male ferrets (Mustela putorius furo) were given acute exposures to aerosols of CdCl2 or NaCl via endotracheal tube. Serial evaluations of the thoracic clearance rate of inhaled 99mTc-pentetate aerosols (MMAD = 0.6 microns, sigma g = 1.6) were made before exposure and at fixed time points after toxicant exposure (3 or 6, 24, 48 h, and 5 days after CdCl2). These serial evaluations of 99mTc-pentetate thoracic clearance were conducted at three cadmium intake levels (3, 10, and 30 min exposure to 10 mg/m3 CdCl2) in order to evaluate possible dose-related response relationships. The rate of thoracic clearance of Tc-pentetate was observed to be slowed at 3 h after exposure to CdCl2 aerosol and subsequently increased to well above control rates. The time sequence observed strongly suggests that increased Tc-pentetate clearance rates are indicative of a tissue response or repair process, rather than acute lung injury. Tracheal epithelial penetration of macromolecular tracers was not observed to increase in histological evaluations following serial sacrifice.

Administration, Inhalation↗
PubMed2000

Light scattering characteristics of aerosols at ambient and as a function of relative humidity: Part II--A comparison of measured scattering and aerosol concentrations using statistical models.

The eastern United States national parks experience some of the worst visibility conditions in the nation. To study these conditions, the Southeastern Aerosol and Visibility Study (SEAVS) was undertaken to characterize the size-dependent composition, thermodynamic properties, and optical characteristics of the ambient atmospheric particles. It is a cooperative three-year study that is sponsored by the National Park Service and the Electric Power Research Institute and its member utilities. The field portion of the study was carried out from July 15 to August 25, 1995. The study design, instrumental configuration, and estimation of aerosol types from particle measurements is presented in a companion paper. In the companion paper, we compare measurements of scattering at ambient conditions and as functions of relative humidity to theoretical predictions of scattering. In this paper, we make similar comparisons, but using statistical techniques. Statistically derived specific scattering associated with sulfates suggest that a reasonable estimate of sulfate scattering can be arrived at by assuming nominal dry specific scattering and treating the aerosols as an external mixture with ammoniation of sulfate accounted for and by the use of Tang's growth curves to predict water absorption. However, the regressions suggest that the sulfate scattering may be underestimated by about 10%. Regression coefficients on organics, to within the statistical uncertainty of the model, suggest that a reasonable estimate of organic scattering is about 4.0 m2/g. A new analysis technique is presented, which does not rely on comparing measured to model estimates of scattering to evoke an understanding of ambient aerosol growth properties, but rather relies on measurements of scattering as a function of relative humidity to develop actual estimates of f(RH) curves. The estimates of the study average f(RH) curve for sulfates compares favorably with the theoretical f(RH) curve for ammonium bisulfate, which is in turn consistent with the study average sulfate ammoniation corresponding to a molar ratio of NH4/SO4 of approximately one. The f(RH) curve for organics is not significantly different from one, suggesting that organics are weakly to nonhygroscopic.

Aerosols↗
PubMedDate not supplied

Chemical and microphysical characterization of ambient aerosols with the aerodyne aerosol mass spectrometer.

The application of mass spectrometric techniques to the real-time measurement and characterization of aerosols represents a significant advance in the field of atmospheric science. This review focuses on the aerosol mass spectrometer (AMS), an instrument designed and developed at Aerodyne Research, Inc. (ARI) that is the most widely used thermal vaporization AMS. The AMS uses aerodynamic lens inlet technology together with thermal vaporization and electron-impact mass spectrometry to measure the real-time non-refractory (NR) chemical speciation and mass loading as a function of particle size of fine aerosol particles with aerodynamic diameters between approximately 50 and 1,000 nm. The original AMS utilizes a quadrupole mass spectrometer (Q) with electron impact (EI) ionization and produces ensemble average data of particle properties. Later versions employ time-of-flight (ToF) mass spectrometers and can produce full mass spectral data for single particles. This manuscript presents a detailed discussion of the strengths and limitations of the AMS measurement approach and reviews how the measurements are used to characterize particle properties. Results from selected laboratory experiments and field measurement campaigns are also presented to highlight the different applications of this instrument. Recent instrumental developments, such as the incorporation of softer ionization techniques (vacuum ultraviolet (VUV) photo-ionization, Li+ ion, and electron attachment) and high-resolution ToF mass spectrometers, that yield more detailed information about the organic aerosol component are also described.

Journal Article↗
PubMed1990

Two-month comparative study of tulobuterol aerosol versus fenoterol aerosol in patients with chronic obstructive lung disease.

In this two month, double-blind, crossover study, the efficacy and safety of tulobuterol aerosol (400 micrograms qid) was compared to fenoterol aerosol (400 micrograms qid) in patients with chronic obstructive lung disease. Thirty-six (36) adults with reversible bronchospasm were enrolled. All patients were evaluable. On set of response was within 5 minutes for both drugs. Mean increases in FEV1 were greater after tulobuterol than fenoterol at every time interval. Increases peaked at 30-60 minutes postdose. Duration of response was longer after tulobuterol with mean FEV1 remaining greater than 15% over baseline for at least 6 hours postdose. Mean predose FEV1 values were significantly greater after 2 and 4 weeks of tulobuterol treatment compared with fenoterol. Despite these large increases, changes in mean FEV1 from predose to 1 hour postdose at these visits were not significantly different between treatment groups. Results of plethysmography testing also indicated greater improvement after tulobuterol. In addition, improvement in pulmonary symptoms was more pronounced during tulobuterol therapy. Small changes in mean blood pressure occurred, with greater changes after fenoterol than after tulobuterol. Changes in mean pulse rate were significantly greater following fenoterol administration. No adverse reactions were reported during tulobuterol treatment; however, one patient experienced severe tremor, tachycardia, and sweating during fenoterol treatment and withdrew from the study prematurely. The results in this study indicate that tulobuterol aerosol is more effective than fenoterol aerosol in the treatment of patients with chronic obstructive lung disease, with fewer cardiovascular effects and no adverse reactions.

Administration, Inhalation↗
PubMed2004

Daily concentrations of trace metals in aerosols in Beijing, China, determined by using inductively coupled plasma mass spectrometry equipped with laser ablation analysis, and source identification of aerosols.

This paper describes the daily concentrations of trace metals and ionic constituents in the aerosol of Beijing, China from March 2001 to August 2003. Daily PM10 concentrations were also measured from September 2001 to August 2003. The daily average PM10 concentration at Beijing, China from September 2001 to August 2003 was 171+/-117 microg m(-3) (n = 673), which is 5-fold higher than at Yokohama, Japan. Trace metal concentrations were analyzed by using inductively coupled plasma mass spectrometry equipped with a laser ablation sample introduction (LA/ICP-MS), which is a rapid and simultaneous method for multi-element analysis. The daily average metal concentrations in TSP in Beijing from March 2001 to August 2003 were: Al: 3.5+/-2.4 (n = 727), Ti: 0.47+/-0.35 (n = 720), V: 0.013+/-0.010 (n = 716), Cr: 0.019+/-0.015 (n = 618), Mn: 0.24+/-0.16 (n = 730), Fe: 5.5+/-3.9 (n = 728), Co: 0.0046+/-0.0055 (n = 629), Ni: 0.022+/-0.024 (n = 680), Cu: 0.11+/-0.11 (n = 660), Zn: 0.77+/-0.60 (n = 726), As: 0.048+/-0.047 (n = 731), Se: 0.010+/-0.010 (n = 550), Cd: 0.0068+/-0.0082 (n = 709), Sb: 0.033+/-0.036 (n = 687), and Pb: 0.43+/-0.50 (n = 728) (unit, microg m(-3)). All the metal concentrations in TSP in Beijing, China were 1.7-21.8 times higher than those in TSP in the center of Tokyo, Japan. Notably, As concentrations in TSP in Beijing were 20-fold higher than those in Tokyo. Source identification of aerosols in Beijing was carried out by using the chemical mass balance (CMB) receptor model, with the daily concentration of metals in the aerosol. The major primary sources of the aerosol of Beijing were considered to be soil dust and coal combustion. Vehicle exhaust contribution tended to increase.

Journal Article↗
PubMed2006

Relationship between indoor and outdoor bio-aerosols collected with a button inhalable aerosol sampler in urban homes.

This field study investigated the relationship between indoor and outdoor concentrations of airborne actinomycetes, fungal spores, and pollen. Air samples were collected for 24 h with a button inhalable aerosol sampler inside and outside of six single-family homes located in the Cincinnati area (overall, 15 pairs of samples were taken in each home). The measurements were conducted during three seasons - spring and fall 2004, and winter 2005. The concentration of culturable actinomycetes was mostly below the detection limit. The median indoor/outdoor ratio (I/O) for actinomycetes was the highest: 2.857. The indoor of fungal and pollen concentrations followed the outdoor concentrations while indoor levels were mostly lower than the outdoor ones. The I/O ratio of total fungal spores (median=0.345) in six homes was greater than that of pollen grains (median=0.025). The low I/O ratios obtained for pollen during the peak ambient pollination season (spring) suggest that only a small fraction penetrated from outdoor to indoor environment. This is attributed to the larger size of pollen grains. Higher indoor concentration levels and variability in the I/O ratio observed for airborne fungi may be associated with indoor sources and/or higher outdoor-to-indoor penetration of fungal spores compared to pollen grains. Practical Implication This study addresses the relationship between indoor and outdoor concentrations of three different types of bio-aerosols, namely actinomycetes, fungal spores, and pollen grains. The results show that actinomycetes are rare in indoor and outdoor air in Midwest, USA. Exposure to pollen occurs mainly in the outdoor air even during peak pollen season. Unexpectedly high fungal spore concentrations were measured outdoors during winter. The presented pilot database on the inhalable levels of indoor and outdoor bio-aerosols can help apportion and better characterize the inhalation exposure to these bio-aerosols. Furthermore, the data can be incorporated into existing models to quantify the penetration of biological particles into indoor environments from outdoors.

Actinomyces↗
PubMed2005

Analysis of shipboard aerosol optical thickness measurements from multiple sunphotometers aboard the R/V Ronald H. Brown during the Aerosol Characterization Experiment--Asia.

Marine sunphotometer measurements collected aboard the R/V Ronald H. Brown during the Aerosol Characterization Experiment-Asia (ACE-Asia) are used to evaluate the ability of complementary instrumentation to obtain the best possible estimates of aerosol optical thickness and Angstrom exponent from ships at sea. A wide range of aerosol conditions, including clean maritime conditions and highly polluted coastal environments, were encountered during the ACE-Asia cruise. The results of this study suggest that shipboard hand-held sunphotometers and fast-rotating shadow-band radiometers (FRSRs) yield similar measurements and uncertainties if proper measurement protocols are used and if the instruments are properly calibrated. The automated FRSR has significantly better temporal resolution (2 min) than the hand-held sunphotometers when standard measurement protocols are used, so it more faithfully represents the variability of the local aerosol structure in polluted regions. Conversely, results suggest that the hand-held sunphotometers may perform better in clean, maritime air masses for unknown reasons. Results also show that the statistical distribution of the Angstrom exponent measurements is different when the distributions from hand-held sunphotometers are compared with those from the FRSR and that the differences may arise from a combination of factors.

Journal Article↗
PubMed2003

Evaluation of nose-only aerosol inhalation chamber and comparison of experimental results with mathematical simulation of aerosol deposition in mouse lungs.

In vivo small rodent efficacy testing of new synthetic and biological molecules for the pulmonary route requires an efficient delivery device. For this purpose, a nose-only inhalation chamber was used to deliver aerosolized aqueous compounds to the respiratory tract of mice. The aim of the study was to determine the efficiency of dose delivery and deposition in the lungs of the mice using this chamber. A secondary goal was to compare the experimental lung deposition results with values predicted from mathematical simulation. Experimental tests were conducted by generating aerosols of a radiolabeled formulation of human serum albumin (HSA) with a mass median aerodynamic diameter (MMAD) of 3.9 +/- 0.5 microm and a geometric standard deviation (GSD) of 1.43 +/- 0.05 using PARI LC STAR jet nebulizers. Based on the total activity placed in the nebulizer, the chamber delivered 0.108 +/- 0.027% to the mice and 0.0087 +/- 0.0021% to the lungs of the mice. In vivo lung deposition was found to be 8.19 +/- 3.56% of total activity deposited in the mouse. Mathematical simulation predictions ranged between 5.89 and 4.40% for various breathing patterns, and did not differ significantly from the in vivo results (p > 0.10). These results provide important quantitative information relevant to aerosol delivery experiments in mouse models. Our results also suggest that the nose-only inhalation chamber would benefit from significant changes to increase the efficiency of deposition in mice such that it can be used for nebulization of expensive therapeutic drugs.

Administration, Inhalation↗
PubMed2001

Aerosolization of cationic lipid-DNA complexes: lipoplex characterization and optimization of aerosol delivery conditions.

This study deals with the development of gene therapy in the treatment of lung diseases. It reports on the use of ultrasonic nebulization to administer plasmid-lipid complexes to the lungs of mice to transfect their epithelial cells. A plasmid complexed to cationic lipids was aerosolized using an ultrasonic nebulizer. We then characterized the lipoplex size and visualized the lipoplex by electron microscopy. Finally, we assessed the in vivo transgene expression in the lungs further to the aerosolization of different lipid-plasmid formulations. The nebulizer-generated particles were small and looked like a string composed of little and more or less cubic units. Transgene expression was detected in the lungs of mice further to a 20-min exposure to aerosol particles produced with the ultrasonic nebulizer. The results obtained with our optimized plasmid-lipid-NaCl formulation suggest that this route can be used to administer an appropriate gene to the airways for the treatment of respiratory disorders.

Administration, Inhalation↗
PubMed1986

Synergistic interaction of ozone and respirable aerosols on rat lungs. II. Synergy between ammonium sulfate aerosol and various concentrations of ozone.

Pulmonary responses after continuous exposure of rats to concentrations of ozone (O3) ranging from 0.12 to 0.64 ppm were quantified by measuring tissue collagen synthesis rate, tissue protein and DNA content, and various constituents of bronchoalveolar lavage fluid. After 7 days of exposure to 0.64 ppm of O3, lung collagen synthesis rate and tissue content of protein and DNA were elevated. After shorter durations of exposure to 0.64 ppm of O3, significant elevations were observed in the protein content and the activities of lactate dehydrogenase, acid phosphatase, and N-acetyl-beta-D-glucosaminidase from lavage fluid. After exposure of rats to 0.20 ppm of O3 for 7 days, changes could be detected in both lung collagen synthesis rate and tissue protein content. Total lavagable protein content, a sensitive indicator for O3-induced effects upon the lung, was significantly elevated in lungs of rats exposed to 0.12 or 0.20 ppm of O3. To examine whether a synergistic interaction occurred between 0.20 or 0.64 ppm of O3 and acid aerosols, rats were continuously exposed to O3 with and without concurrent exposure to 5 mg/m3 of ammonium sulfate. A synergistic interaction between 0.20 ppm of O3 and ammonium sulfate aerosol was observed by measurement of total lavagable protein and of lung collagen synthesis rate. These results demonstrate that ammonium sulfate aerosol interacts synergistically with O3 at concentrations of O3 that approach ambient levels.

Aerosols↗