Respaud R.,University of Tours |
Respaud R.,French Institute of Health and Medical Research |
Marchand D.,University of Tours |
Marchand D.,French Institute of Health and Medical Research |
And 22 more authors.
Journal of Controlled Release | Year: 2016
The high toxicity of ricin and its ease of production have made it a major bioterrorism threat worldwide. There is however no efficient and approved treatment for poisoning by ricin inhalation, although there have been major improvements in diagnosis and therapeutic strategies. We describe the development of an anti-ricin neutralizing monoclonal antibody (IgG 43RCA-G1) and a device for its rapid and effective delivery into the lungs for an application in humans. The antibody is a full-length IgG and binds to the ricin A-chain subunit with a high affinity (KD = 53 pM). Local administration of the antibody into the respiratory tract of mice 6 h after pulmonary ricin intoxication allowed the rescue of 100% of intoxicated animals. Specific operational constraints and aerosolization stresses, resulting in protein aggregation and loss of activity, were overcome by formulating the drug as a dry-powder that is solubilized extemporaneously in a stabilizing solution to be nebulized. Inhalation studies in mice showed that this formulation of IgG 43RCA-G1 did not induce pulmonary inflammation. A mesh nebulizer was customized to improve IgG 43RCA-G1 deposition into the alveolar region of human lungs, where ricin aerosol particles mostly accumulate. The drug delivery system also comprises a semi-automatic reconstitution system to facilitate its use and a specific holding chamber to maximize aerosol delivery deep into the lung. In vivo studies in monkeys showed that drug delivery with the device resulted in a high concentration of IgG 43RCA-G1 in the airways for at least 6 h after local deposition, which is consistent with the therapeutic window and limited passage into the bloodstream. © 2016
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.
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 15 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.
Verma N.K.,Trinity College Dublin |
Crosbie-Staunton K.,Trinity College Dublin |
Satti A.,Trinity College Dublin |
Gallagher S.,Trinity College Dublin |
And 8 more authors.
Journal of Nanobiotechnology | Year: 2013
Background: Aerosolized therapeutics hold great potential for effective treatment of various diseases including lung cancer. In this context, there is an urgent need to develop novel nanocarriers suitable for drug delivery by nebulization. To address this need, we synthesized and characterized a biocompatible drug delivery vehicle following surface coating of Fe3O4 magnetic nanoparticles (MNPs) with a polymer poly(lactic-co-glycolic acid) (PLGA). The polymeric shell of these engineered nanoparticles was loaded with a potential anti-cancer drug quercetin and their suitability for targeting lung cancer cells via nebulization was evaluated.Results: Average particle size of the developed MNPs and PLGA-MNPs as measured by electron microscopy was 9.6 and 53.2 nm, whereas their hydrodynamic swelling as determined using dynamic light scattering was 54.3 nm and 293.4 nm respectively. Utilizing a series of standardized biological tests incorporating a cell-based automated image acquisition and analysis procedure in combination with real-time impedance sensing, we confirmed that the developed MNP-based nanocarrier system was biocompatible, as no cytotoxicity was observed when up to 100 μg/ml PLGA-MNP was applied to the cultured human lung epithelial cells. Moreover, the PLGA-MNP preparation was well-tolerated in vivo in mice when applied intranasally as measured by glutathione and IL-6 secretion assays after 1, 4, or 7 days post-treatment. To imitate aerosol formation for drug delivery to the lungs, we applied quercitin loaded PLGA-MNPs to the human lung carcinoma cell line A549 following a single round of nebulization. The drug-loaded PLGA-MNPs significantly reduced the number of viable A549 cells, which was comparable when applied either by nebulization or by direct pipetting.Conclusion: We have developed a magnetic core-shell nanoparticle-based nanocarrier system and evaluated the feasibility of its drug delivery capability via aerosol administration. This study has implications for targeted delivery of therapeutics and poorly soluble medicinal compounds via inhalation route. © 2013 Verma et al.; licensee BioMed Central Ltd.
PubMed | Institute Of Recherche Biomedicale Des Armees Irba Crssa, Directorate General of Armaments, New York University, LFB Biotechnologies and 7 more.
Type: | Journal: Journal of controlled release : official journal of the Controlled Release Society | Year: 2016
The high toxicity of ricin and its ease of production have made it a major bioterrorism threat worldwide. There is however no efficient and approved treatment for poisoning by ricin inhalation, although there have been major improvements in diagnosis and therapeutic strategies. We describe the development of an anti-ricin neutralizing monoclonal antibody (IgG 43RCA-G1) and a device for its rapid and effective delivery into the lungs for an application in humans. The antibody is a full-length IgG and binds to the ricin A-chain subunit with a high affinity (KD=53pM). Local administration of the antibody into the respiratory tract of mice 6h after pulmonary ricin intoxication allowed the rescue of 100% of intoxicated animals. Specific operational constraints and aerosolization stresses, resulting in protein aggregation and loss of activity, were overcome by formulating the drug as a dry-powder that is solubilized extemporaneously in a stabilizing solution to be nebulized. Inhalation studies in mice showed that this formulation of IgG 43RCA-G1 did not induce pulmonary inflammation. A mesh nebulizer was customized to improve IgG 43RCA-G1 deposition into the alveolar region of human lungs, where ricin aerosol particles mostly accumulate. The drug delivery system also comprises a semi-automatic reconstitution system to facilitate its use and a specific holding chamber to maximize aerosol delivery deep into the lung. In vivo studies in monkeys showed that drug delivery with the device resulted in a high concentration of IgG 43RCA-G1 in the airways for at least 6h after local deposition, which is consistent with the therapeutic window and limited passage into the bloodstream.
News Article | November 23, 2016
MarketStudyReport.com adds “Pneumatic Nebulizers Market Size By Product (Breath-Actuated, Vented), Industry Analysis Report, Regional Outlook (U.S., Canada, UK, Germany, France, Spain, Italy, Japan, China, India, South Africa, Brazil, Mexico), Unit Shipments, Application Potential, Price Trends, Competitive Market Share & Forecast, 2016-2023” new report to its research database. The report spread across 190 pages with table and figures in it. Global Pneumatic Nebulizers Market size was valued at $626.21 million for 2015 and is predicted to register CAGR of more than 6% during forecast timeline. Increasing occurrence of respiratory problems like COPD(chronic obstructive pulmonary disease), rising old age population, rapidly altering life patterns and large scale technological innovations are key factors promoting industry growth trends during forecast timeline.Increase in aging population all across the globe is predicted to expand pneumatic nebulizers market share as old persons are susceptible to respiratory problems. Further, there is rising occurrence of respiratory ailments like asthma, bronchitis, chronic obstructive pulmonary disease (COPD) and cystic fibrosis owing to increasing levels of smoking and pollution. Also, respiratory ailments adversely affect individuals as well as their work & workplace along with families. Yearly health care spending on asthma is predicted to be about $20.71 billion. U.S. Pneumatic Nebulizers Market size, by product, 2012 ? 2023 (USD Million) U.S. Pneumatic Nebulizers Market size, by product, 2012 ? 2023 (USD Million) Global pneumatic nebulizers industry is also experiencing many innovations in terms of device size, portability and user friendliness. In other words, technological breakthrough has made device size small and more modernized. Rising device mobility and portability owing to introduction of rechargeable batteries in the business sector is predicted to boost revenue growth. Product Trends The industry is segmented into different products like portable nebulizers, vented nebulizers and breath-actuated nebulizers.Portable nebulizers segment has experienced substantial expansion and is predicted to register CAGR of 7.51% during forecast timeframe. The growth of the segment can be credited to increasing demand for bronchodilator combined treatments. Vented nebulizers dominated the product segment for 2015 with revenue predicted to cross $701 million by end of forecast timeline. Key growth drivers include increasing occurrence of respiratory problems in emerging economies that need inexpensive therapy and easy device integration with different kinds of compressors. In terms of size, this segment is predicted to surpass 7.51 million units mark by end of 2023 and the reason for predicted growth in size being rising amount of patient population and cost efficacy. Breath- actuated nebulizers segment is predicted to register CAGR of 6.31% during forecast timeline. They are popular in industry as they offer aerosol production along with higher medicine delivery, less drug loss and large fine-particle fraction at the time of expiration. Regional Trends Global pneumatic nebulizers industry is segmented into key geographical regions like North America, Latin America, MEA, APAC and Europe.U.S. pneumatic nebulizers market share was more than $200 million for 2015 and the growth can be attributed to factors like quick acceptance of new technology, favorable government policies encouraging early treatment for respiratory ailments and user friendly features of technologically modernized portable equipments.Europe pneumatic nebulizers market is predicted to surpass $301 million mark by end of 2023 and it was driven by Germany in past. The reason being high rate of occurrence of respiratory problems among the population of the country. For example, about 2.71 million of patients are treated for COPD in Germany. APAC pneumatic nebulizers industry is anticipated to register highest CAGR of about 8% during forecast timeline. Increasing proportion of pollution in developing nations coupled with lack of regulations regarding control pollution and fast changing lifestyles has increased occurrence of COPD in this region. Competitive Trends Key industry participants profiled in the report include Briggs Healthcare, Philips Respironics Incorporation, OMRON Corporation, Aerogen Limited, Becton, Dickinson & Company, Philips Respironics, Allied Healthcare Products Incorporation, TaiDoc Technology, Heyer Medial AG, DeVilbiss Healthcare, Salter Labs and PARI Medical Holdings GmbH. To receive personalized assistance, write to us @ [email protected] with the report title in the subject line along with your questions or call us at +1 866-764-2150
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.