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Targeted drug aerosol deposition analysis for a four-generation lung airway model with hemispherical tumors
1Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910, USA. ck@eos.ncsu.edu
Abstract:
One important research area of broad interest is the development of highly efficient drug delivery systems for desired site deposition and uptake. For example, controlled drug aerosol release and targeting to specific regions of the lung is a novel way to combat lung diseases, diabetes, virus infections, cancers, etc. Determination of feasible air-particle streams is a prerequisite for the development of such delivery devices, say, smart inhalers. The concept of "controlled particle release and targeting" is introduced and results are discussed for a representative model of bronchial lung airways afflicted with hemispherical tumors of different sizes and locations. It is shown that under normal particle inlet conditions a particle mass fraction of only up to 11% may deposit on the surface of a specific tumor with critical radius r/R approximately 1.25, while a controlled particle release achieves deposition fractions of 35 to 92% for a realistic combination of inlet Stokes and Reynolds numbers, depending mainly on tumor size. Furthermore, with the controlled release and targeting approach nearby healthy tissue is hardly impacted by the typically aggressive drug aerosols. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting micron-particles in sequentially bifurcating rigid airways, the results were obtained using a validated commercial finite-volume code with user-enhanced programs on a high-end engineering workstation. The new concept is generic and hence should be applicable to other regions of the respiratory system as well.
Insights
Controlled particle release significantly enhances drug deposition in lung tumors, achieving 35-92% efficiency compared to normal delivery. This novel approach minimizes impact on healthy tissue, offering a promising strategy for targeted lung disease treatment.
Area of Science:
- Biomedical Engineering
- Respiratory Medicine
- Drug Delivery Systems
Background:
- Efficient drug delivery to specific lung regions is crucial for treating various diseases.
- Current methods often lack targeted deposition, leading to suboptimal treatment outcomes.
- Smart inhalers require understanding air-particle stream dynamics for controlled release.
Purpose of the Study:
- To introduce and evaluate a novel concept of "controlled particle release and targeting" for drug aerosols in the lungs.
- To determine the feasibility and efficacy of this approach in delivering drugs to lung tumors.
- To assess the impact on healthy lung tissue during targeted drug delivery.
Main Methods:
- Modeling of bronchial lung airways with hemispherical tumors of varying sizes and locations.
- Simulation of air-particle flow using a validated commercial finite-volume code with user-enhanced programs.
- Analysis of particle deposition fractions under normal versus controlled particle release conditions.
Main Results:
- Controlled particle release achieved deposition fractions of 35% to 92%, significantly higher than the 11% under normal conditions.
- Deposition efficiency is primarily dependent on tumor size.
- The controlled release approach minimally affected surrounding healthy lung tissue.
Conclusions:
- The "controlled particle release and targeting" concept demonstrates high efficacy for drug deposition in lung tumors.
- This method offers a significant improvement over conventional delivery, with potential for treating lung diseases.
- The generic nature of the approach suggests applicability to other respiratory system regions.
