Evaluating the bioavailability and therapeutic efficacy of nintedanib-loaded novasomes as a therapy for non-small cell lung cancer

Abstract

Nintedanib (NTD) is a tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer (NSCLC). However, the limited aqueous solubility of oral NTD contributes to its low bioavailability and absorption through the epithelial surface of the airways. A nebulized formulation of NTD-loaded novasomes (NLN) was developed as a potential therapy for NSCLC, with the goal of enhancing the delivery, sustainability, bioavailability, and efficacy of NTD. Utilizing design expert software, various NLN formulations were optimized through Box-Behnken design to pinpoint the optimal formulation. Furthermore, we performed analyses on the aerodynamic properties, cytotoxicity, bioavailability, computed tomography imaging, and toxicity of the optimal NLN formulation. The optimal NLN formulation increased the sustainability and bioavailability of NTD compared to NTD suspension. The aerodynamic properties of the optimal NLN formulation suggest that it is respirable, making it suitable for use as an inhalable delivery carrier. Furthermore, cytotoxicity results indicate that the optimal NLN formulation demonstrates significant pharmacological efficacy in treating lung cancer. The inhaled optimal NLN formulation showed a greater capacity to accumulate NTD in the lungs. The histopathological examination confirmed the safety of the optimal NLN formulation. In conclusion, a nebulized NLN formulation could be a potential therapy for NSCLC.