Improving the bioavailability of nintedanib by formulating inhalable ufasomes as a targeted therapy for non-small cell lung cancer

The safety and effectiveness of nintedanib in treating non-small cell lung cancer (NSCLC) have been evaluated in several clinical trials. However, nintedanib exhibits low oral bioavailability due to its poor solubility and first-pass metabolism. To enhance the sustainability, targeting, bioavailability, and effectiveness of nintedanib, a targeted therapy for NSCLC was developed in the form of nebulized nintedanib ufasomes (NLU). Various NLU formulations were optimized utilizing the Design Expert software. The selected NLU was then evaluated for its aerodynamics, cytotoxicity, bioavailability, and targeting capabilities. To evaluate the effectiveness and safety of the optimal NLU formulation, a dose-dependent study was conducted using a mouse model of lung cancer induced by Lewis lung carcinoma (LLC) cell lines. The selected NLU formulation increased the sustainability, bioavailability, and targeting capability of nintedanib by 49.5 %, 6.63-fold, and 8.99-fold, respectively. Additionally, it decreased the IC₅₀ value by 4.7-fold. The nebulized NLU showed better anti-tumor, anti-inflammatory, and anti-oxidative effects than oral nintedanib in terms of LDH, CEA, AFP, MDA, TNF-α, and IL-1β. The histopathological analysis confirmed these results. The safety and efficacy studies demonstrated that the nebulized NLU formulation at a dose of 100 mg/kg could serve as a viable therapy for NSCLC.