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Low N.,University of Bern | Bavdekar A.,King Edward Memorial Hospital Research Center | Jeyaseelan L.,Christian Medical College | Hirvez S.,Shirdi Sai Baba Hospital | And 13 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND: Aerosolized vaccine can be used as a needle-free method of immunization against measles, a disease that remains a major cause of illness and death. Data on the immunogenicity of aerosolized vaccine against measles in children are inconsistent. METHODS: We conducted an open-label noninferiority trial involving children 9.0 to 11.9 months of age in India who were eligible to receive a first dose of measles vaccine. Children were randomly assigned to receive a single dose of vaccine by means of either aerosol inhalation or a subcutaneous injection. The primary end points were seropositivity for antibodies against measles and adverse events 91 days after vaccination. The noninferiority margin was 5 percentage points. RESULTS: A total of 1001 children were assigned to receive aerosolized vaccine, and 1003 children were assigned to receive subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91, but outcome data were missing for 331 children because of thawed specimens. In the per-protocol population, data on 1560 of 2004 children (77.8%) could be evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785 children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were seropositive, a difference of -9.2 percentage points (95% CI, -12.2 to -6.3). Findings were similar in the full-analysis set (673 of 788 children in the aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%] were seropositive at day 91, a difference of -9.3 percentage points [95% CI, -12.3 to -6.4]) and after multiple imputation of missing results. No serious adverse events were attributable to measles vaccination. Adverse-event profiles were similar in the two groups. CONCLUSIONS: Aerosolized vaccine against measles was immunogenic, but, at the prespecified margin, the aerosolized vaccine was inferior to the subcutaneous vaccine with respect to the rate of seropositivity. (Funded by the Bill and Melinda Gates Foundation; Measles Aerosol Vaccine Project Clinical Trials Registry-India number, CTRI/ 2009/ 091/ 000673.) Copyright © 2015 Massachusetts Medical Society.

Simones M.P.,University of Missouri | Loyalka S.K.,University of Missouri | Duffy C.,Aerogen | MacLoughlin R.,Aerogen | And 2 more authors.
European Journal of Nanomedicine | Year: 2014

The charge distribution of aerosol is an important factor for accurate prediction of aerosol behavior as it influences particle transport, settling, deposition, and coagulation. In the production of aerosol for pulmonary drug delivery, charging of aerosol particles is influenced by both the generation method and chemical properties of the drug. Electrostatic charging of add-on devices such as plastic spacers and holding chambers will reduce the delivery to the lung, while charged particles can also enhance deposition to the respiratory system by inducing an image charge to airway surfaces. Typical target particle size for delivery devices in terms of mass median aerodynamic diameter (MMAD) is 1-5 μm, and therefore up to 50% of the dose includes submicron particles in the fine (100-1000 nm) and ultrafine (<100 nm) size range. Measurement of the charge distribution of submicron particles produced using a vibrating mesh nebulizer is presented using a tandem differential mobility analyzer (TDMA). It is found that the charge distribution is not at equilibrium, but instead has an increase in the fraction of charged particles below 200 nm and a decrease in the charged fraction above 200 nm. In general the charge distribution will be dependent on the specific aerosol nebulizer setup being used and the chemical properties of the nebulized solution, and it could be further quantified by using the methods discussed here. © 2014 by Walter de Gruyter Berlin/Boston.

Galvin P.,Tyndall National Institute | Thompson D.,Tyndall National Institute | Ryan K.B.,University College Cork | McCarthy A.,University College Cork | And 12 more authors.
Cellular and Molecular Life Sciences | Year: 2012

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues. © 2011 Springer Basel AG.

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