A New Pulmonary Drug Targeted Delivery Method for Lung Diseases Treatment: An in-Silico Study

Authors: 
Feng, Y., Oklahoma Center for Respiratory and Infectious Diseases
Haghnegahdar, A., Oklahoma State University
Chen, X., Southeast University
Yang, M., University of Copenhagen
Pulmonary drug delivery therapies, ranging from the treatment of asthma and chronic obstructive pulmonary diseases (COPD) to lung tumors and systemic diseases, have gained considerable interest in recent years. Advantages of pulmonary drug delivery, when compared with conventional medical treatments include improvements in efficiency because of the large surface area of the lung and the thin epithelial layer thickness, reduction of systemic drug levels with a decrease in adverse effects, and higher degree of convenience. However, existing delivery methodologies still have poor efficiencies (<25%) for directing drugs to the localized lung diseases sites. Major portions of the aggressive medicine deposit on healthy tissues, which causes severe side effects and induces extra health care expenses. In light of the high cost of medicine and potentially devastating side-effects of drug treatment, the development of a new targeted drug delivery methodology is of great clinical significance. In this study, a new pulmonary drug targeted delivery method, i.e., “controlled air-drug stream injection,” is proposed and validated by the numerical study of drug particle transport and deposition in subject-specific human upper airway systems using a Computational Fluid-Particle Dynamics (CFPD) model. Results indicate that, by manipulating geometric and operation parameters, physicians can use the new method and a new drug delivery device based on the electronic-cigarette design to achieve 100% drug delivery into a specific lung lobe. Parameters that significantly influence the air-drug streams are identified, i.e., particle-release locations and timing, drug aerosol properties, breathe pattern, and morphological differences of human upper airways. Specifically, simulations based on the natural conservation laws generate high-resolution data of the airflow and drug particle transport and deposition from mouth to lung lobes. Particle release maps provide guidance on patient-specific clinical operations to direct drug particles to the diseased lobes, and thereby enhance treatment efficacy, protect patients from undesired side effects, and reduce the healthcare cost. This research represents the first known effort to use EC designs to create a new drug delivery method to target lung disease lesions with simulations in realistic human respiratory system configurations. As the preclinical study, the computational work provides non-invasive high-resolution data for patient-specific drug transport and deposition, a critical step towards translational work needed to maximize the efficiency of animal studies, to develop animal-to-human transfer functions, and to test development in clinical trials. This work is expected to support wider applications for creating new targeting strategies in combating a broad range of lung and systemic diseases.