Pulmonary drug delivery and retention: a computational study to identify plausible parameters based on a coupled airway-mucus flow model

TL;DR

This study develops a coupled airway-mucus flow model to analyze pulmonary drug delivery, identifying optimal aerosol sizes and breathing conditions for effective deep lung targeting, which can improve drug efficacy and reduce side effects.

Contribution

It introduces a computational model that couples aerosol transport and mucus flow to optimize pulmonary drug delivery parameters for deep lung targeting.

Findings

Aerosols of 1-5 μm are most effective for deep lung delivery.

Doubling breathing time increases drug deposition in deep lungs by a factor of 2.

Breath control can enhance drug delivery efficacy and reduce required dosage.

Abstract

Pulmonary drug delivery systems rely on inhalation of drug-laden aerosols produced from aerosol generators such as inhalers, nebulizers etc. On deposition, the drug molecules diffuse in the mucus layer and are also subjected to mucociliary advection which transports the drugs away from the initial deposition site. The availability of the drug at a particular region of the lung is, thus, determined by a balance between these two phenomena. A mathematical analysis of drug deposition and retention in the lungs is developed through a coupled mathematical model of aerosol transport in air as well as drug molecule transport in the mucus layer. The mathematical model is solved computationally to identify suitable conditions for the transport of drug-laden aerosols to the deep lungs. This study identifies the conditions conducive for delivering drugs to the deep lungs which is crucial for achieving systemic drug delivery. The effect of different parameters on drug retention is also characterized for various regions of the lungs, which is important in determining the availability of the inhaled drugs at a target location. Our analysis confirms that drug delivery efficacy remains highest for aerosols in the size range of 1-5 $\mu$m. Moreover, it is observed that amount of drugs deposited in the deep lung increases by a factor of 2 when the breathing time period is doubled, with respect to normal breathing, suggesting breath control as a means to increase the efficacy of drug delivery to the deep lung. A higher efficacy also reduces the drug load required to be inhaled to produce the same health effects and hence, can help in minimizing the side effects of a drug.