title: Smart lipid nanoparticles containing levofloxacin and DNase for lung delivery. Design and characterization.
abstract: Levofloxacin (LV) is a hydrophilic broad-spectrum antibiotic commonly used in pulmonary treatment against recurrent infections of Pseudomonas aeruginosa, and particularly in cystic fibrosis (CF) disease. In order to study feasible carriers for LV, solid lipid nanoparticles (SLN) of myristyl myristate were prepared by the ultrasonication method in the presence of Pluronic(®)F68 under different experimental conditions and characterized by dynamic light scattering, optical, transmission and scanning electron microscopy for size and morphology. Alternatively, nanostructured lipid carriers (NLCs) were developed to improve LV encapsulation and storage. SLN showed 20.1±1.4% LV encapsulation efficiency, while the NLCs encapsulated 55.9±1.6% LV. NLC formulation exhibited a more controlled release profile than SLN formulation, but both showed a biphasic drug release pattern with burst release at the first 5h and prolonged release afterwards, demonstrated by in vitro tests. The hydrodynamic average diameter and zeta potential of NLC were 182.6±3.2nm and -10.2±0.2mV, respectively, and were stable for at least 3 months. Additionally, DNase type I was incorporated into the formulations as a "smart" component, since the enzyme could help to decrease the viscoelasticity found in the lungs of CF patients and improves the antibiotic diffusion. FTIR, XRD, DSC, TGA and nitrogen adsorption isotherms of the nanoparticles indicate the presence of the loads in a noncrystalline state. The developed formulation showed an active antimicrobial activity against P. aeruginosa and even against other opportunistic pathogens such as Staphylococcus aureus. The presence of LV-loaded NLCs reduced the formation of a bacterial biofilm, which highlighted the significance of the nanodevice as a new alternative for CF treatment.
authors.affiliation: Nanobiomaterials Laboratory, Institute of Applied Biotechnology CINDEFI (UNLP-CONICET, CCT La Plata), Dept. of Chemistry, School of Sciences, Universidad Nacional de La Plata, Calle 47y 115, La Plata 1900, Argentina.
authors.forename: Germán A
authors.initials: GA
authors.lastname: Islan
authors.affiliation: Nanobiomaterials Laboratory, Institute of Applied Biotechnology CINDEFI (UNLP-CONICET, CCT La Plata), Dept. of Chemistry, School of Sciences, Universidad Nacional de La Plata, Calle 47y 115, La Plata 1900, Argentina; Instituto de Investigaciones en Ciencia y Tecnología de Materiales (INTEMA, Universidad Nacional de Mar del Plata, CONICET), Mar del Plata, Argentina.
authors.forename: Pablo Cortez
authors.initials: PC
authors.lastname: Tornello
authors.affiliation: Instituto de Investigaciones en Ciencia y Tecnología de Materiales (INTEMA, Universidad Nacional de Mar del Plata, CONICET), Mar del Plata, Argentina.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Abraham
authors.affiliation: Institute of Chemistry, Biological Chemistry Laboratory, Universidade Estadual de Campinas, C.P. 6159, CEP 13083-970 Campinas, SP, Brazil; Brazilian Nanotechnology National Laboratory (LNNano-CNPEM), Campinas, SP, Brazil.
authors.forename: Nelson
authors.initials: N
authors.lastname: Duran
authors.affiliation: Nanobiomaterials Laboratory, Institute of Applied Biotechnology CINDEFI (UNLP-CONICET, CCT La Plata), Dept. of Chemistry, School of Sciences, Universidad Nacional de La Plata, Calle 47y 115, La Plata 1900, Argentina. Electronic address: grcastro@gmail.com.
authors.forename: Guillermo R
authors.initials: GR
authors.lastname: Castro
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002152:Calorimetry, Differential Scanning; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D003851:Deoxyribonucleases / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D006801:Humans; D064704:Levofloxacin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008055:Lipids; D064704:Levofloxacin; D003851:Deoxyribonucleases
keywords: Cystic fibrosis; DNase; Levofloxacin; Nanostructured lipid carriers; Pulmonary delivery; Solid lipid nanoparticles