Micromaterials lipid-based for topic release of fluticasone propionate for the COPD treatment

Oxidative stress is instrumental in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). It is a serious lung disease, characterized by fatal breathing problems due to smoking-related airway inflammation that have arisen by excessive quantities of reactive oxigen species (ROS). Chronic exposure to ROS causes bronchial inflammation, reduced air flow, and smoking-induced airway epithelial cell death. Drug delivery to the lungs by inhalation has got an increasing interest in the biomedical field as a method of non-invasive drug. Microparticles, being inhalation drug carriers, have found to be effective for high deposition in lung epithelium. In fact, the their large size (> 2 ?m size) decreases the probability of phagocytic clearance from the lung periphery and increases particle retention time in the lung [3] necessary for the longer therapeutic duration. In particular, our group has developed two pharmaceutical formulations using biocompatible lipids decorated with chitosan and alginate for sustained release of fluticasone propionate (FP) into the lungs. The presence of mucoadhesive polymers allows SLMs to adhere better to the mucous layer on the respiratory epithelium as compared with conventional carriers. The obtained systems are characterized in terms of size, polydispersity index (PDI), zeta potential and morphology. We also evaluated the loading capacity (LC) as well as the kinetics release. Afterwards, we evaluated the cytotoxicity in vitro of the free FP or entrapped into SLMs and empty microparticles by MTS viability assays on 16-HBE (human bronchial epithelial cells) cell lines. Neither FP-loaded SLMs nor empty SLMs at the different tested concentrations showed cytotoxicity compared to the free FP. Finally, we tested the effect of CSE (cigarette smoke extract) in ROS production by bronchial epithelial cells evaluating the expression of survivin and p-erk/tot-erk ratio. FP-loaded SLM significantly reduced survivin expression and p-erk/tot-erk expression ratio.