title: Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis.
abstract: Lung impairment is the most life-threatening factor for cystic fibrosis patients. Indeed, Pseudomonas aeruginosa is the main pathogen in the pulmonary infection of these patients. In this work, we developed sodium colistimethate loaded lipid nanoparticles, namely, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), as a strategy to enhance the antimicrobial therapy against P. aeruginosa in cystic fibrosis patients. The nanoparticles obtained displayed a 200-400 nm size, high drug entrapment (79-94%) and a sustained drug release profile. Moreover, both SLN and NLC presented antimicrobial activity against clinically isolated P. aeruginosa. The integrity of the nanoparticles was not affected by nebulization through a mesh vibrating nebulizer. Moreover, lipid nanoparticles appeared to be less toxic than free sodium colistimethate in cell culture. Finally, an in vivo distribution experiment showed that nanoparticles spread homogenously through the lung and there was no migration of lipid nanoparticles to other organs, such as liver, spleen or kidneys.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country, 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: marta.pastor@ehu.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Pastor
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country, 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: maria.moreno@ehu.es.
authors.forename: María
authors.initials: M
authors.lastname: Moreno-Sastre
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country, 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: amaia.esquisabel@ehu.es.
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: Daniel
authors.initials: D
authors.lastname: Bachiller
authors.affiliation: Fundación Investigaciones Sanitarias Islas Baleares (FISIB), Development and Regeneration Program, Ctra. Sóller km 12, Bunyola (Balearic Islands) 07110, Spain.
authors.forename: Víctor José
authors.initials: VJ
authors.lastname: Asensio
authors.affiliation: B.R.A.I.E., Hermanos Lumiere 5, Miñao 01510, Spain.
authors.forename: Angel Del
authors.initials: AD
authors.lastname: Pozo
authors.affiliation: B.R.A.I.E., Hermanos Lumiere 5, Miñao 01510, Spain.
authors.forename: Eusebio
authors.initials: E
authors.lastname: Gainza
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country, 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; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003091:Colistin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000382:microbiology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008055:Lipids; C004691:colistinmethanesulfonic acid; D003091:Colistin
keywords: Cystic fibrosis; Lipid nanoparticles; NLC; Nanomedicine; Pseudomonas aeruginosa; Sodium colistimethate