Investigating the Potential of Ufasomes Laden with Nintedanib as an Optimized Targeted Lung Nanoparadigm for Accentuated Tackling of Idiopathic Pulmonary Fibrosis

<b>Background/objectives</b>: Idiopathic pulmonary fibrosis (IPF) is a prevalent interstitial lung disease that typically progresses gradually, leading to respiratory failure and ultimately death. IPF can be treated with the tyrosine kinase inhibitor, nintedanib (NTD), owing to its anti-fibrotic properties, which ameliorate the impairment of lung function. This study aimed to formulate, optimize, and assess NTD-loaded ufasomes (NTD-UFSs) as a nanosystem for its pulmonary targeting to snowball the bioavailability and therapeutic efficacy of the drug. <b>Methods</b>: To investigate the influence of numerous factors on NTD-UFSs assembly and to determine the optimal formulation, Box-Behnken statistical design was implemented with the assistance of Design-Expert^® software. The thin-film hydration strategy was employed to fabricate NTD-UFSs. The optimum NTD-UFSs formulation was subsequently selected and subjected to additional evaluations. Also, using a rat model, a comparative pharmacokinetic analysis was scrutinized. <b>Results</b>: The optimal NTD-UFSs elicited an accumulative release of 65.57% after 24 h, an encapsulation efficiency of 62.51%, a zeta potential of -36.07 mV, and a vesicular size of 364.62 nm. In addition, it disclosed remarkable stability and a continuous cumulative release pattern. In vivo histopathological studies ascertained the tolerability of NTD-UFSs administered intratracheally. According to the pharmacokinetic studies, intratracheal NTD-UFSs administration manifested a significantly higher AUC_0-∞ value than oral and intratracheal NTD suspensions, by approximately 5.66- and 3.53-fold, respectively. <b>Conclusions</b>: The findings of this study proposed that UFSs might be a promising nanoparadigm for the non-invasive pulmonary delivery of NTD.