title: Multifunctional polymeric nanoparticles doubly loaded with SPION and ceftiofur retain their physical and biological properties.
abstract: BACKGROUND
  Advances in nanostructure materials are leading to novel strategies for drug delivery and targeting, contrast media for magnetic resonance imaging (MRI), agents for hyperthermia and nanocarriers. Superparamagnetic iron oxide nanoparticles (SPIONs) are useful for all of these applications, and in drug-release systems, SPIONs allow for the localization, direction and concentration of drugs, providing a broad range of therapeutic applications. In this work, we developed and characterized polymeric nanoparticles based on poly (3-hydroxybutyric acid-co-hydroxyvaleric acid) (PHBV) functionalized with SPIONs and/or the antibiotic ceftiofur. These nanoparticles can be used in multiple biomedical applications, and the hybrid SPION-ceftiofur nanoparticles (PHBV/SPION/CEF) can serve as a multifunctional platform for the diagnosis and treatment of cancer and its associated bacterial infections.
  
  
  RESULTS
  Morphological examination using transmission electron microscopy (TEM) showed nanoparticles with a spherical shape and a core-shell structure. The particle size was evaluated using dynamic light scattering (DLS), which revealed a diameter of 243.0 ± 17 nm. The efficiency of encapsulation (45.5 ± 0.6% w/v) of these polymeric nanoparticles was high, and their components were evaluated using spectroscopy. UV-VIS, FTIR and DSC showed that all of the nanoparticles contained the desired components, and these compounds interacted to form a nanocomposite. Using the agar diffusion method and live/dead bacterial viability assays, we demonstrated that these nanoparticles have antimicrobial properties against Escherichia coli, and they retain their magnetic properties as measured using a vibrating sample magnetometer (VSM). Cytotoxicity was assessed in HepG2 cells using live/dead viability assays and MTS, and these assays showed low cytotoxicity with IC50 > 10 mg/mL nanoparticles.
  
  
  CONCLUSIONS
  Our results indicate that hybrid and multifunctional PHBV/SPION/CEF nanoparticles are suitable as a superparamagnetic drug delivery system that can guide, concentrate and site-specifically release drugs with antibacterial activity.
authors.affiliation: Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science, Echaurren 183, Santiago, Chile. paula.solar@unab.cl.|Departamento de Ciencias y Tecnología Farmacéutica, Universidad de Chile, Facultad de Ciencias Químicas y Farmacéuticas, Santos Dumont 964, Independencia, Santiago, Chile. paula.solar@unab.cl.
authors.forename: Paula
authors.initials: P
authors.lastname: Solar
authors.affiliation: Center for the Development of Nanoscience and Nanotechnology, CEDENNA, 9170124, Av. Ecuador 3493, Estación Central, Santiago, Chile. ggonzale@uchile.cl.|Departamento de Química, Laboratorio de Síntesis Inorgánica y Electroquímica, Universidad de Chile, Facultad de Ciencias, Las Palmeras 3425, Nuñoa, Santiago, Chile. ggonzale@uchile.cl.
authors.forename: Guillermo
authors.initials: G
authors.lastname: González
authors.affiliation: Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science, Echaurren 183, Santiago, Chile. cvilos@gmail.com.|Center for the Development of Nanoscience and Nanotechnology, CEDENNA, 9170124, Av. Ecuador 3493, Estación Central, Santiago, Chile. cvilos@gmail.com.
authors.forename: Cristian
authors.initials: C
authors.lastname: Vilos
authors.affiliation: Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science, Echaurren 183, Santiago, Chile. natalia.herrera@unab.cl.
authors.forename: Natalia
authors.initials: N
authors.lastname: Herrera
authors.affiliation: Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science, Echaurren 183, Santiago, Chile. natalia.juica@unab.cl.
authors.forename: Natalia
authors.initials: N
authors.lastname: Juica
authors.affiliation: Center for the Development of Nanoscience and Nanotechnology, CEDENNA, 9170124, Av. Ecuador 3493, Estación Central, Santiago, Chile. mabel.moreno@gmail.com.
authors.forename: Mabel
authors.initials: M
authors.lastname: Moreno
authors.affiliation: Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, República 252, Santiago, Chile. fsimon@unab.cl.|Facultad de Medicina, Universidad Andres Bello, República 590, Santiago, Chile. fsimon@unab.cl.|Millennium Institute on Immunology and Immunotherapy, Avenida Libertador Bernardo O'Higgins 340, Santiago, Chile. fsimon@unab.cl.
authors.forename: Felipe
authors.initials: F
authors.lastname: Simon
authors.affiliation: Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science, Echaurren 183, Santiago, Chile. luis.velasquez@unab.cl.|Center for the Development of Nanoscience and Nanotechnology, CEDENNA, 9170124, Av. Ecuador 3493, Estación Central, Santiago, Chile. luis.velasquez@unab.cl.
authors.forename: Luis
authors.initials: L
authors.lastname: Velásquez
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002511:Cephalosporins / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D004926:Escherichia coli / Q000187:drug effects; D005290:Ferric Compounds / Q000737:chemistry*; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011108:Polymers; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D000094122:Polyhydroxybutyrates
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D011091:Polyesters; D011108:Polymers; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates; C000499:ferric oxide; C053503:ceftiofur