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Islan, G.A.; Ruiz, M.E.; Morales, J.F.; Sbaraglini, M.L.; Enrique, A.V.; Burton, G.; Talevi, A.; Bruno-Blanch, L.E.; Castro, G.R. "Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: Physicochemical characterization and in vivo targeted delivery to the lungs" (2017) Journal of Materials Chemistry B. 5(17):3132-3144
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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. © The Royal Society of Chemistry 2017.

Registro:

Documento: Artículo
Título:Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: Physicochemical characterization and in vivo targeted delivery to the lungs
Autor:Islan, G.A.; Ruiz, M.E.; Morales, J.F.; Sbaraglini, M.L.; Enrique, A.V.; Burton, G.; Talevi, A.; Bruno-Blanch, L.E.; Castro, G.R.
Filiación:Laboratorio de Nanobiomateriales, CINDEFI - Departamento de Química, Universidad Nacional de la Plata, Calles 47 y 115, La Plata, Buenos Aires, B1900AJI, Argentina
Cátedra de Control de Calidad de Medicamentos, Departamento de Ciencias Biológicas, Universidad Nacional de la Plata, Calles 47 y 115, La Plata, Buenos Aires, B1900AJI, Argentina
Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB), Departamento de Ciencias Biológicas, Universidad Nacional de la Plata, Calles 47 y 115, La Plata, Buenos Aires, B1900AJI, Argentina
Departamento de Química Orgánica and UMYMFOR (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Piso 3, Intendente Gúiraldes 2160, Buenos Aires, C1428EGA, Argentina
Palabras clave:Antibiotics; Crystalline materials; Drug products; Gas adsorption; Scanning electron microscopy; Controlled drug release; Morphological characterization; Narrow size distributions; Nitrogen adsorption isotherm; Physico-chemical characterization; Pseudomonas aeruginosa; Pulmonary administrations; Recurrent pulmonary infection; Controlled drug delivery
Año:2017
Volumen:5
Número:17
Página de inicio:3132
Página de fin:3144
DOI: http://dx.doi.org/10.1039/c6tb03366k
Título revista:Journal of Materials Chemistry B
Título revista abreviado:J. Mater. Chem. B
ISSN:20507518
CODEN:JMCBD
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20507518_v5_n17_p3132_Islan

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Citas:

---------- APA ----------
Islan, G.A., Ruiz, M.E., Morales, J.F., Sbaraglini, M.L., Enrique, A.V., Burton, G., Talevi, A.,..., Castro, G.R. (2017) . Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: Physicochemical characterization and in vivo targeted delivery to the lungs. Journal of Materials Chemistry B, 5(17), 3132-3144.
http://dx.doi.org/10.1039/c6tb03366k
---------- CHICAGO ----------
Islan, G.A., Ruiz, M.E., Morales, J.F., Sbaraglini, M.L., Enrique, A.V., Burton, G., et al. "Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: Physicochemical characterization and in vivo targeted delivery to the lungs" . Journal of Materials Chemistry B 5, no. 17 (2017) : 3132-3144.
http://dx.doi.org/10.1039/c6tb03366k
---------- MLA ----------
Islan, G.A., Ruiz, M.E., Morales, J.F., Sbaraglini, M.L., Enrique, A.V., Burton, G., et al. "Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: Physicochemical characterization and in vivo targeted delivery to the lungs" . Journal of Materials Chemistry B, vol. 5, no. 17, 2017, pp. 3132-3144.
http://dx.doi.org/10.1039/c6tb03366k
---------- VANCOUVER ----------
Islan, G.A., Ruiz, M.E., Morales, J.F., Sbaraglini, M.L., Enrique, A.V., Burton, G., et al. Hybrid inhalable microparticles for dual controlled release of levofloxacin and DNase: Physicochemical characterization and in vivo targeted delivery to the lungs. J. Mater. Chem. B. 2017;5(17):3132-3144.
http://dx.doi.org/10.1039/c6tb03366k