Pulmonary Surfactant-Based Paclitaxel-Loaded Nanovesicles for Inhalation Therapy of Lung Adenocarcinoma

Abstract

Treatments for lung adenocarcinoma, a type of non-small-cell lung cancer that accounts for about 40% of all lung cancers, are generally administered intravenously, thus causing systemic side effects and poor pulmonary delivery. Inhalation therapy has been investigated to overcome these limitations; however, it shows limited delivery of drugs to the distal lung region, rapid clearance by alveolar macrophages, and immune responses due to synthetic materials. In this study, we developed inhalable nanotherapeutics to treat lung adenocarcinoma using exogenous pulmonary surfactant (PS) that are lipid-based, clinically used, and easy to fuse with the endogenous PS layer in the alveolar space. We prepared PS-based nanovesicles (PSNVs) using the thin-film hydration method followed by extrusion. PSNVs interacted selectively with alveolar type II cell-derived adenocarcinoma cells in vitro and retained long in the alveolar space of mice after inhalation, presumably due to the incorporated PS proteins. Furthermore, inhalation treatments of paclitaxel-loaded PSNVs significantly inhibited the tumor growth in the lungs of the orthotopic lung cancer mouse model established by intratracheally injection of A549 cells into nude mice, compared with free paclitaxel and paclitaxel-loaded synthetic NVs. These results suggest that the use of PSNVs for inhalation delivery of a wide range of therapeutic agents has great potential for the treatment of various lung diseases, including lung adenocarcinoma.