Integrated in vitro experimental modelling of inhaled drug delivery: deposition, dissolution and absorption

This article reviews the state-of-the-art for in vitro experimental modelling involving the deposition of respirable particles onto respiratory epithelial cells for the purpose of studying inhalation biopharmaceutics (e.g., particle uptake or translocation, drug dissolution, metabolism or absorption). Original research is reported to illustrate the issues involved in delivering respirable particles to epithelial cells in a way that replicates deposition in the lung in vivo. The adaptation of the cascade centripeter, a virtual impactor, is described. This apparatus was used to deposit salmeterol xinafoate (SX) particles with different size, shape and polymorphic composition onto the surface of air-interfaced Calu-3 respiratory epithelial cells. In this instance, no measurable difference in absorptive transfer was detected between the two types of SX particle. Dose rather than particle characteristics determined the rate of drug transfer, indicating that there is unlikely to be any value in terms of post-deposition processes in modifying the particle characteristics for this particular drug. The technique described represents a ‘physiologically-relevant’ method of particle presentation to airway cells and provides an opportunity to investigate biopharmaceutical processes in a lung-like environment without some of the expense and complexity associated with undertaking whole animal studies. The article concludes by considering future directions for integrative in vitro modeling of the fate of particles after deposition in the lung.