title: Pulmonary delivery of tobramycin-loaded nanostructured lipid carriers for Pseudomonas aeruginosa infections associated with cystic fibrosis.
abstract: Among the pathogens that affect cystic fibrosis (CF) patients, Pseudomonas aeruginosa is the most prevalent. As a way to fight against this infection, nanotechnology has emerged over the last decades as a promising alternative to overcome resistance to antibiotics in infectious diseases. The goal of this work was to elaborate and characterize lipid nanoparticles for pulmonary delivery of tobramycin. Tobramycin-loaded nanostructured lipid carriers (Tb-NLCs) were prepared by hot melt homogenization technique. In addition, nanoparticles labeled with infrared dye (IR-NLCs) were used to investigate their in vivo performance after pulmonary administration. Tb-NLCs displayed a mean diameter size around 250 nm, high drug encapsulation (93%) and sustained release profile. Tb-NLCs showed to be active against clinically isolated P. aeruginosa. Moreover, Tb-NLCs did not decrease cell viability and were able to overcome an artificial mucus barrier in the presence of mucolytics agents. During the in vivo assay, IR-NLCs were administered to several mice by the intratracheal route using a Penn Century device. Next, the biodistribution of the nanoparticles was analyzed at different time points showing a wide nanosystem distribution in the lungs. Altogether, tobramycin-loaded NLCs seem to us an encouraging alternative to the currently available CF therapies.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Moreno-Sastre
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pastor
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: Amaia
authors.initials: A
authors.lastname: Esquisabel
authors.affiliation: Department of Pathology and Experimental Therapeutics, Medical School, University of Barcelona - IDIBELL, Barcelona, Spain.
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Sans
authors.affiliation: Department of Pathology and Experimental Therapeutics, Medical School, University of Barcelona - IDIBELL, Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Viñas
authors.affiliation: Fundación Investigaciones Sanitarias Islas Baleares (FISIB), Development and Regeneration Program, Ctra. Sóller km 12, Bunyola (Balearic Islands) 07110, Spain; Consejo Superior de Investigaciones Científicas (CSIC), Ctra. Sóller km 12, Bunyola (Balearic Islands) 7110, Spain.
authors.forename: Aarne
authors.initials: A
authors.lastname: Fleischer
authors.affiliation: Fundación Investigaciones Sanitarias Islas Baleares (FISIB), Development and Regeneration Program, Ctra. Sóller km 12, Bunyola (Balearic Islands) 07110, Spain; Consejo Superior de Investigaciones Científicas (CSIC), Ctra. Sóller km 12, Bunyola (Balearic Islands) 7110, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Palomino
authors.affiliation: Fundación Investigaciones Sanitarias Islas Baleares (FISIB), Development and Regeneration Program, Ctra. Sóller km 12, Bunyola (Balearic Islands) 07110, Spain; Consejo Superior de Investigaciones Científicas (CSIC), Ctra. Sóller km 12, Bunyola (Balearic Islands) 7110, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bachiller
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain. Electronic address: joseluis.pedraz@ehu.es.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D008055:Lipids; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000008:administration & dosage*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D014031:Tobramycin / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D008055:Lipids; D014031:Tobramycin
keywords: Cystic fibrosis; Lipid nanoparticles; Nanocarriers; Pseudomonas aeruginosa; Pulmonary administration; Tobramycin