In vivo integrity of polymer-coated gold nanoparticles.

Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties may change upon internalization by cells. While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles ((198)Au) and engineered an (111)In-labelled polymer shell around them. Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for (198)Au and (111)In showed partial removal of the polymer shell in vivo. While (198)Au accumulates mostly in the liver, part of the (111)In shows a non-particulate biodistribution similar to intravenous injection of chelated (111)In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even nanoparticles with high colloidal stability can change their physicochemical properties in vivo.

Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.

Endotoxin (Lipopolysaccharide, LPS) is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease.In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and 20 µg LPS to the airways and 5 µg LPS to the alveoli using controlled aerosol bolus inhalation. Inflammatory parameters were assessed during a 72 h time period. LPS deposited in the airways induced dose dependent systemic responses with increases of blood neutrophils (peaking at 6 h), Interleukin-6 (peaking at 6 h), body temperature (peaking at 12 h), and CRP (peaking at 24 h). 5 µg LPS targeted to the alveoli caused significantly stronger effects compared to 5 µg airway LPS deposition. Local responses were studied by measuring lung function (FEV(1)) and reactive oxygen production, assessed by hydrogen peroxide (H(2)O(2)) in fractionated exhaled breath condensate (EBC). FEV(1) showed a dose dependent decline, with lowest values at 12 h post LPS challenge. There was a significant 2-fold H(2)O(2) induction in airway-EBC at 2 h post LPS inhalation. Alveolar LPS targeting resulted in the induction of very low levels of EBC-H(2)O(2).Targeting LPS to the alveoli leads to stronger systemic responses compared to airway LPS targeting. Targeted LPS inhalation may provide a novel model of airway inflammation for studying the role of LPS contamination of air pollution in lung diseases, exacerbation and anti-inflammatory drugs.

Fractionated exhaled breath condensate collection shows high hydrogen peroxide release in the airways.

BACKGROUND: Exhaled breath condensate (EBC) allows noninvasive monitoring of inflammation in the lung. Activation of inflammatory cells results in an increased production of reactive oxygen species, leading to the formation of hydrogen peroxide (H(2)O(2)). In addition, cigarette smoking causes an influx of inflammatory cells, and higher levels of H(2)O(2) have been found in EBC of smokers. However, there are still unresolved issues reflected by large variations in exhaled H(2)O(2) and uncertainties about the origin of H(2)O(2) release in the lung. METHODS: We collected EBC as fractionated samples from the airways and from the lung periphery in 10 nonsmokers, eight asymptomatic smokers, and in eight chronic obstructive pulmonary disease (COPD) patients, and H(2)O(2) concentration and acidity (pH) were analyzed in the airway and the alveolar fraction. RESULTS: In all subjects studied, H(2)O(2) was 2.6 times higher in the airway versus the alveolar fraction. Airway H(2)O(2) was twofold higher in smokers and fivefold higher in COPD patients compared to nonsmokers. In all study groups, there was no significant difference in deaerated pH between the airway and the alveolar sample. CONCLUSIONS: Exhaled H(2)O(2) is released at higher concentrations from the airways of all subjects studied, implying that the airways may be the dominant location of H(2)O(2) production. Because many lung diseases cause inflammation at different sites of the lung, fractionated sampling of EBC can reduce variability and maintain an anatomical allocation of the exhaled biomarkers.

Pulsating aerosols for drug delivery to the sinuses in healthy volunteers.

OBJECTIVE: Approximately 10 to 15 percent of the European and U.S. population have chronic rhinosinusitis, but effective treatment remains a challenge. There has been limited success using topical drug delivery to the nose and the paranasal cavities/sinuses, in part because most nasally administered aerosol drug formulations are efficiently filtered at the nasal valve and fail to reach the osteomeatal area and sinuses. STUDY DESIGN: Feasibility study. SETTING: Nuclear medicine department. SUBJECTS AND METHODS: Pulsating airflows were applied to the nasal cavity and sinus ventilation was studied in five healthy human volunteers using dynamic (81m)Kr-gas gamma camera imaging. Furthermore, deposition and retention of (99m)Tc-DTPA radiolabeled aerosols delivered by nasal pump sprays or by pulsating aerosols was assessed in each volunteer over a 24-hour period. RESULTS: Only the pulsating airflow demonstrated efficient (81m)Kr-gas ventilation of the paranasal sinuses. No drug was deposited into the sinuses using nasal pump sprays, but up to 6.5 percent of the nasally administered drug was deposited into the sinuses using pulsating airflow. Clearance kinetics of the drug was reduced after pulsating aerosol delivery compared to nasal pump sprays. Residence time of the drug at the site of deposition was up to three-fold longer with pulsating aerosol delivery than with nasal pump sprays. CONCLUSION: Our data support the hypothesis that topical drug delivery in relevant quantities to the nose and osteomeatal areas, including the paranasal sinuses, is possible using pulsating airflows. Furthermore, the frequency of drug applications may be reduced due to a delayed clearance and longer residence time.