Vismodegib-loaded ufasomes inhaler for treatment of non-small cell lung cancer

Vismodegib (VIS) is a selective inhibitor of the hedgehog pathway that targets tumor progenitor cells and inhibits clonogenic development in non-small cell lung cancer (NSCLC). However, VIS has poor aqueous solubility and a highly hydrophobic nature, leading to extremely low bioavailability and limiting its clinical utility when administered orally. This study's primary objective was to improve the bioavailability, safety, and effectiveness of VIS in mitigating NSCLC by developing a VIS-loaded ufasomes (VLU) inhaler. Using the Box-Behnken design, several VLU formulations were optimized. The aerodynamic characteristics and cell viability of the optimal VLU formulation were evaluated. Additionally, the bioavailability, efficacy, and safety of the inhaled VLU were examined in a mouse model of Lewis lung carcinoma to assess its potential in treating lung cancer. The optimal VLU formulation achieved a 74.62% reduction in the release rate of VIS. Additionally, it resulted in a 4.87-fold decrease in A549 cell viability and a 4.42-fold increase in the bioavailability of VIS. Moreover, the optimal VLU enhanced the aerodynamic characteristics of VIS. The inhaled VLU led to significant reductions in lactate dehydrogenase, carcinoembryonic antigen, and alpha-fetoprotein levels, with decreases of 92.43%, 95.06%, and 97.02%, respectively, when compared to the disease group. Additionally, toxicity and histopathological studies confirmed the efficacy and safety of the inhaled VLU. The inhaled VLU shows promise as an effective and safe treatment option for NSCLC.