Design of a smart nanoformulations based on levofloxacin-loaded nanostructured lipid carriers (NLC) and DNase for cystic fibrosis lung delivery

G. ISLAN; P.R. CORTEZ TORNELLO; G.A. ABRAHAM; G.R. CASTRO; N. DURAN

COLLOIDS AND SURFACES B-BIOINTERFACES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 143 p. 168 - 176

0927-7765

Levofloxacin (LV) is a hydrophilic broad-spectrum antibiotic commonly used in pulmonary treatmentagainst recurrent infections of Pseudomonas aeruginosa, and particularly in cystic fibrosis (CF) disease. Inorder to study feasible carriers for LV, solid lipid nanoparticles (SLN) of myristyl myristate were preparedby the ultrasonication method in the presence of Pluronic®F68 under different experimental conditionsand characterized by dynamic light scattering, optical, transmission and scanning electron microscopyfor size and morphology. Alternatively, nanostructured lipid carriers (NLCs) were developed to improveLV encapsulation and storage. SLN showed 20.1 ± 1.4% LV encapsulation efficiency, while the NLCs encap-sulated 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 5 h and prolonged releaseafterwards, demonstrated by in vitro tests. The hydrodynamic average diameter and zeta potential of NLCwere 182.6 ± 3.2 nm and −10.2 ± 0.2 mV, 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 couldhelp 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 theloads in a noncrystalline state. The developed formulation showed an active antimicrobial activity againstP. aeruginosa and even against other opportunistic pathogens such as Staphylococcus aureus. The presenceof LV-loaded NLCs reduced the formation of a bacterial biofilm, which highlighted the significance of thenanodevice as a new alternative for CF treatment.