Realizing Lobe-Specific Aerosol Targeting in a 3D-Printed <i>In Vitro</i> Lung Model

Abstract

Background: Delivery of aerosols to isolated lobes of the lungs would be beneficial for diseases that have lobe-specific effects, such as cancer, pneumonia, and chronic obstructive pulmonary disorder. Recent computational fluid-particle dynamic (CFPD) modeling has demonstrated that in low flow rates, the inlet location of a particle at the mouth dictates the lobe into which it will deposit. However, realization of this lobe-specific deposition has yet to be attempted experimentally or in the clinic. To address this, we sought to develop a proof-of-concept in vitro model and targeting device for achieving lobe-specific delivery. Methods: Using 3D printing, a lung replica was created from a computed tomography scan of a healthy 47-year-old male volunteer and connected to a flow setup to control inlet flow rate and outlet airflow distribution to each lobe. A device was designed and fabricated that directs particles to an inlet location that is 5% of the total inlet area and described by radial coordinates ( r , θ ). Filter paper at sampling ports for each lobe was used to capture fluorescent polystyrene particles to quantify particle collection. We evaluated lobe-specific targeting at varied inlet coordinates, particle diameters, inlet flow rates, and disease lobe flow rate distribution profiles. Results: Guided by CFPD modeling, inlet locations were identified that increased particle collection to a target lobe between 63% and 90%. For example, release of fluorescent particles at the inlet location r = 4.67 mm, θ = 252° with respect to the center of the inlet using 1 μm particles, 1 L/min inlet flow rate, and healthy subject lobe flow distribution profile yielded 90% of the aerosol dose to the right upper lobe, corresponding to an increase of 4.6 × above the non-targeted percent particle collection. Particle size, inlet flow rate, and disease airflow distributions were all shown to generally decrease the efficiency of lobe-specific targeting. Conclusions: Our results indicate that aerosol targeting of a specific lobe is possible in vitro under optimized conditions and that controlling inlet locations could be a potentially useful method for treatment of lobe-specific diseases. This is the first demonstration of lobe-specific particle collection in a physical lung model and illuminates numerous challenges that will be faced as this method is translated to clinical applications.

Topics & Concepts