A simple pulmonary retention model accounting for dissolution and macrophage-mediated removal of deposited polydisperse particles

This article describes a mechanistic two-compartmental model to simulate the disposition by dissolution and particulate clearance of particles deposited in the pulmonary region of the lung. The model provides a general solution for the size distribution of particles in the surfactant layer of the alveolar surface and in the cell plasma of alveolar macrophages. Thus it allows for different dissolution rates in the two compartments and accounts for potentially different kinetics and/or biological effects of particles and their solute in surrounding fluids. The input parameters are, among others, the size distribution density function of the deposited particles and the time constants characterizing the dissolution process as well as phagocytosis rate and particle transport by macrophages to the tracheobronchial tract. Relevant dose parameters such as retained and dissolved mass can be calculated from the temporally retained size distributions. For the first time, this theoretical presentation considers the polydispersity of aerosol particles deposited in the lung and thus provides an indispensable mathematical basis for a multicompartmental retention model that may combine particulate removal from the pulmonary region and the lymph nodes by a competition of the rates of dissolution and particulate clearance in all relevant lung model compartments.