title: A theoretical compartment model for antigen kinetics in the skin.
abstract: 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.
authors.affiliation: Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, the Netherlands. Electronic address: a.m.romgens@tue.nl.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Römgens
authors.affiliation: Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, the Netherlands; Faculty of Health Sciences, University of Southampton, Southampton SO17 1BJ, UK.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Bader
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, the Netherlands.
authors.forename: Joke A
authors.initials: JA
authors.lastname: Bouwstra
authors.affiliation: Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, the Netherlands.
authors.forename: Cees W J
authors.initials: CW
authors.lastname: Oomens
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008845:Microinjections; D008954:Models, Biological; D009339:Needles; D011956:Receptors, Cell Surface / Q000378:metabolism; D012867:Skin / Q000378:metabolism*
chemical_list: D000941:Antigens; D011956:Receptors, Cell Surface
keywords: Antigen uptake; Pharmacokinetic model; Skin kinetics; Vaccine delivery