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

Aranyak Chakravarty, Mahesh V Panchagnula, Alladi Mohan and Neelesh A Patankar

PLOS Computational Biology, 2022, vol. 18, issue 6, 1-15

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 μm. 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.Author summary: Pulmonary drug delivery systems utilize the respiratory mechanism to directly deliver drugs to a target region of the lungs. The drug molecules deposit in the mucus lining, on reaching the target region, and are simultaneously transported away from the target region due to mucociliary transport and molecular diffusion. The availability of drugs at a target lung region and hence, efficacy of the drugs, therefore, determined by the delivery and retention of the drugs at the target region. The present study computationally solves the coupled transport equations to identify the conditions conducive for drug delivery and retention in the deep lungs. Drug delivery efficacy to the deep lung is observed to be highest for 1–5 μm aerosols. Breathing time period is also observed to influence efficacy. The amount of drugs deposited in the deep lung is observed to increase by a factor of 2 when the breathing time period is doubled with respect to normal breathing period. Such insights gained from this analysis will potentially help in devising mechanisms for increasing drug availability in the deep lung which is essential in achieving systemic drug delivery.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1010143

DOI: 10.1371/journal.pcbi.1010143

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