Loading of Beclomethasone in Liposomes and Hyalurosomes Improved with Mucin as Effective Approach to Counteract the Oxidative Stress Generated by Cigarette Smoke Extract

In this work beclomethasone dipropionate was loaded into liposomes and hyalurosomesmodified with mucin to improve the ability of the payload to counteract the oxidative stress andinvolved damages caused by cigarette smoke in the airway. The vesicles were prepared by dispersingall components in the appropriate vehicle and sonicating them, thus avoiding the use of organicsolvents. Unilamellar and bilamellar vesicles small in size (~117 nm), homogeneously dispersed(polydispersity index lower than 0.22) and negatively charged (~?11 mV), were obtained. Moreover,these vesicle dispersions were stable for five months at room temperature (~25 C). In vitro studiesperformed using the Next Generation Impactor confirmed the suitability of the formulations to benebulized as they were capable of reaching the last stages of the impactor that mimic the deeperairways, thus improving the deposition of beclomethasone in the target site. Further, biocompatibilitystudies performed by using 16HBE bronchial epithelial cells confirmed the high biocompatibilityand safety of all the vesicles. Among the tested formulations, only mucin-hyalurosomes werecapable of effectively counteracting the production of reactive oxygen species (ROS) induced bycigarette smoke extract, suggesting that this formulation may represent a promising tool to reduce thedamaging effects of cigarette smoke in the lung tissues, thus reducing the pathogenesis of cigarettesmoke-associated diseases such as chronic obstructive pulmonary disease, emphysema, and cancer