Achieving Targeted Delivery of Chemotherapeutic Particles to Small Airway Tumors via Pulmonary Route Using Endotracheal Catheters: A CFPD Study

Abstract

Tracheobronchial tumors, while uncommon, are often malignant in adults. Surgical removal is the primary therapy for non-metastatic lung malignancies, but it is only possible in a small percentage of non-small-cell lung cancer patients and is limited by the number and location of tumors, as well as the patient’s overall health. This study proposes an alternative treatment: administering aerosolized chemotherapeutic particles via the pulmonary route using endotracheal catheters to target lung tumors. To improve delivery efficiency to the lesion, it is essential to understand local drug deposition and particle transport dynamics. This study uses an experimentally validated computational fluid particle dynamics (CFPD) model to simulate the transport and deposition of inhaled chemotherapeutic particles in a 3-dimensional tracheobronchial tree with 10 generations (G). Based on the particle release maps, targeted drug delivery strategies are proposed to enhance particle deposition at two lung tumor sites in G10. Results indicate that controlled drug release can improve particle delivery efficiencies at both targeted regions. The use of endotracheal catheters significantly affects particle delivery efficiencies in targeted tumors. The parametric analysis shows that using smaller catheters can deliver more than 74% of particles to targeted tumor sites, depending on the location of the tumor and the catheter diameter used, compared to less than 1% using conventional particle administration methods. Furthermore, the results indicate that particle release time has a significant impact on particle deposition under the same inhalation profile. This study serves as a first step in understanding the impact of catheter diameter on localized endotracheal injection for targeting tumors in small lung airways.

Computational fluid dynamics modeling of aerosol particle transport through lung airway mucosa

“…The stationary solution is a major simplification of the physiological case, but such simulations are useful as they take a comparatively short time to compute and show long-term trends, most notably the concentration profiles. Targeted deposition technologies allow for drug to be concentrated in a single lobe of the lung ( Islam and Feng, 2023 ), but the dosage is otherwise dispersed across a large surface area. A user may tune the model to fit the type of dispersal that is expected, such as using a time-dependent parabolic distribution function for the inlet rather than a constant concentration; this route potentially increases rigor at the cost of increased computational times and residual errors.…”

“…Even with our simplified technique proposed here, future users can extend the work to consider tapering dosages along sequential segments of an expanded dosage region. For more intricate models of inhaled particle dispersal and transport in the airways, see the work of Feng and colleagues ( Kleinstreur and Feng, 2013 ; Feng et al, 2018 , 2019 ; Kolewe et al, 2021 ; Islam and Feng, 2023 ).…”