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dc.contributor.author
Islan, German Abel  
dc.contributor.author
Ruiz, María Esperanza  
dc.contributor.author
Morales, Juan Francisco  
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Sbaraglini, Maria Laura  
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Enrique, Andrea Verónica  
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Burton, Gerardo  
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Talevi, Alan  
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Bruno Blanch, Luis Enrique  
dc.contributor.author
Castro, Guillermo Raul  
dc.date.available
2018-08-07T19:19:07Z  
dc.date.issued
2016-03  
dc.identifier.citation
Islan, German Abel; Ruiz, María Esperanza; Morales, Juan Francisco; Sbaraglini, Maria Laura; Enrique, Andrea Verónica; et al.; Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: Physicochemical characterization and in vivo targeted delivery to the lungs; Royal Society of Chemistry; Journal of Materials Chemistry B; 5; 17; 3-2016; 3132-3144  
dc.identifier.issn
2050-750X  
dc.identifier.uri
http://hdl.handle.net/11336/54475  
dc.description.abstract
Current medical treatments against recurrent pulmonary infections caused by Pseudomonas aeruginosa, such as cystic fibrosis (CF) disorder, involve the administration of inhalable antibiotics. The main challenge is, however, the eradication of microbial biofilms immersed in dense mucus that requires high and recurrent antibiotic doses. Accordingly, the development of novel drug delivery systems capable of providing local and controlled drug release in the lungs is a key factor to improve the therapeutic outcome of such therapeutic molecules. Inhalable hybrid carriers were prepared by co-precipitation of CaCO3 in the presence of alginate and the resulting microparticles were treated with alginate lyase (AL) in order to modify their porosity and enhance the drug loading. The hybrid microparticles were loaded with DNase (mucolytic agent) and levofloxacin (LV, wide-spectrum antibiotic) in the range of 20-40% for LV and 28-67% for DNase, depending on the AL treatment. In vitro studies demonstrated that microparticles were able to control the DNase release for 24 h, while 30-50% of LV was released in 3 days. The morphological characterization was performed by optical, fluorescence and scanning electron microscopies, showing a narrow size distribution (5 mm). FTIR, XRD, DSC and nitrogen adsorption isotherm studies revealed the presence of the drugs in a non-crystalline state. A microcidal effect of microparticles was found on P. aeruginosa in agar plates and corroborated by Live/Dead kit and TEM observations. Finally, to study whether the microparticles improved the localization of LV in the lungs, in vivo studies were performed by pulmonary administration of microparticles to healthy mice via nebulization and dry powder inhalation, followed by the quantification of LV in lung tissue. The results showed that microparticles loaded with LV delivered the antibiotic at least 3 times more efficiently than free LV. The developed system opens the gateway to new drug delivery systems that may provide enhanced therapeutic solutions against bacterial infections and in particular as a potential tool in CF pathology.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Royal Society of Chemistry  
dc.rights
info:eu-repo/semantics/restrictedAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Alginate  
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Calcium Carbonate  
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Cystic Fibrosis  
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Controlled Release  
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Dnase  
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Inhalable Antibiotics  
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Levofloxacin  
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Local Therapy  
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Microparticles  
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Pulmonary Delivery  
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Nano-materiales  
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Nanotecnología  
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INGENIERÍAS Y TECNOLOGÍAS  
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Otras Ciencias de la Salud  
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Ciencias de la Salud  
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CIENCIAS MÉDICAS Y DE LA SALUD  
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Otras Ciencias Biológicas  
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Ciencias Biológicas  
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CIENCIAS NATURALES Y EXACTAS  
dc.title
Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: Physicochemical characterization and in vivo targeted delivery to the lungs  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-08-06T17:42:59Z  
dc.journal.volume
5  
dc.journal.number
17  
dc.journal.pagination
3132-3144  
dc.journal.pais
Reino Unido  
dc.journal.ciudad
Londres  
dc.description.fil
Fil: Islan, German Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina  
dc.description.fil
Fil: Ruiz, María Esperanza. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Morales, Juan Francisco. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Enrique, Andrea Verónica. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Burton, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina  
dc.description.fil
Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina  
dc.description.fil
Fil: Bruno Blanch, Luis Enrique. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas; Argentina  
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Fil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina  
dc.journal.title
Journal of Materials Chemistry B  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1039/c6tb03366k  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2017/TB/C6TB03366K