A theoretical compartment model for antigen kinetics in the skin

The skin is a promising location for vaccination with its abundant population of
antigen capturing and presenting cells. The development of new techniques, such
as the use of microneedles, can facilitate the delivery of vaccines into the
skin. In recent years, many different types of microneedle arrays have been
designed. However, their geometry and arrangement within an array may be
optimized to trigger sufficient antigen presenting cells. A computational model
can support the rational design of microneedle arrays. Therefore, the aim of the
current study was to describe the distribution and kinetics of a delivered
antigen within the skin using a theoretical compartment model, which included
binding of antigens to receptors and their uptake by cells, and to determine
which parameters should be measured to validate the model for a specific
application. Multiple simulations were performed using a high and low antigen
delivery dose and a range of values for the rate constants. The results
indicated that the cells were highly saturated when a high dose was applied,
while for a low dose saturation was only reached in 5% of the simulations. This
was caused by the difference in the ratio between the administered dose and the
available binding sites and suggests the dose should be adapted to the number of
cells and receptors for a specific compound. The sensitivity analysis of the
model parameters confirmed that the initial dose and receptor concentrations
were indeed the two parameters that had the largest influence on the variance in
antigen concentrations within the cells and circulation at equilibrium. Hence,
these parameters are important to be measured in vivo. The presented
pharmacokinetics model can be used in future computational models to predict the
influence of microneedle array geometry to optimize their design.