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

## TL;DR

This study improves nintedanib's effectiveness for lung cancer by creating an inhalable formulation that boosts drug delivery and reduces side effects.

## Contribution

A novel nebulized ufasome formulation of nintedanib is developed to enhance bioavailability and targeting for non-small cell lung cancer.

## Key findings

- The NLU formulation increased nintedanib's bioavailability by 6.63-fold and targeting capability by 8.99-fold.
- NLU showed better anti-tumor and anti-inflammatory effects than oral nintedanib in a mouse model.
- The optimal NLU dose of 100 mg/kg demonstrated safety and efficacy in treating NSCLC.

## Abstract

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.

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