Abstract
Lung cancer is the leading cause of cancer death. Many studies have shown the beneficial effects of Atorvastatin in decreasing the mortality risk and improving survival among patients with lung cancer. This research paper focuses on improving AVT cytotoxic activity and cellular uptake by developing mannitol microcarriers as a promising drug delivery system for lung cancer treatment and, studying the impact of improving inhalation deposition on the delivery and Dry Powder formulations efficiency. The AVT loaded mannitol (AM) microparticles (AVT-AM) formulation was prepared by spray drying and characterized for its physicochemical properties and aerodynamic deposition. The results revealed that the AVT-AM formulation has good flow properties and aerosol deposition with a particle size of 3418 nm ± 26.86. The formulation was also assessed in vitro for cytotoxicity effects (proliferation, apoptosis, and cell cycle progression) on A549 human lung adenocarcinoma. Compared with free AVT, the AVT-AM formulation has significantly higher cellular uptake and anti-cancer properties by disrupting cell cycle progression via either apoptosis or cell cycle arrest in the G2/M phase. This study shows that AVT loaded mannitol microcarriers may provide a potentially effective and sustained pulmonary drug delivery for lung cancer treatment.