A theoretical compartment model for antigen kinetics in the skin
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.
pharmacokinetic model, antigen uptake, skin kinetics, vaccine delivery
18-25
Römgens, Anne M.
95ac7f7a-6ccb-478b-92cf-bfc779d815b7
Bader, Dan
9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
Bouwstra, Joke A.
48afb1ce-12e5-4ee9-85c9-54d390fe1ca6
Oomens, Cees W.J.
e8a85b85-3719-4909-9f82-4f03d8a43263
10 March 2016
Römgens, Anne M.
95ac7f7a-6ccb-478b-92cf-bfc779d815b7
Bader, Dan
9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
Bouwstra, Joke A.
48afb1ce-12e5-4ee9-85c9-54d390fe1ca6
Oomens, Cees W.J.
e8a85b85-3719-4909-9f82-4f03d8a43263
Römgens, Anne M., Bader, Dan, Bouwstra, Joke A. and Oomens, Cees W.J.
(2016)
A theoretical compartment model for antigen kinetics in the skin.
European Journal of Pharmaceutical Sciences, 84, .
(doi:10.1016/j.ejps.2016.01.007).
(PMID:26776970)
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.
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Accepted/In Press date: 6 January 2016
e-pub ahead of print date: 9 January 2016
Published date: 10 March 2016
Keywords:
pharmacokinetic model, antigen uptake, skin kinetics, vaccine delivery
Organisations:
Faculty of Health Sciences
Identifiers
Local EPrints ID: 390214
URI: http://eprints.soton.ac.uk/id/eprint/390214
ISSN: 0928-0987
PURE UUID: 003a7391-e17f-41ec-b5e2-4d5db8203d75
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Date deposited: 22 Mar 2016 12:06
Last modified: 14 Mar 2024 23:14
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Contributors
Author:
Anne M. Römgens
Author:
Joke A. Bouwstra
Author:
Cees W.J. Oomens
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