A theoretical compartment model for antigen kinetics in the skin
| Autor: | AM Anne Römgens, Cwj Cees Oomens, Joke A. Bouwstra, Dan L. Bader |
|---|---|
| Přispěvatelé: | Soft Tissue Biomech. & Tissue Eng. |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Vaccine delivery Microinjections 0206 medical engineering Population Pharmaceutical Science Receptors Cell Surface 02 engineering and technology SDG 3 – Goede gezondheid en welzijn Models Biological 03 medical and health sciences Pharmacokinetics Antigen SDG 3 - Good Health and Well-being In vivo Animals Humans Distribution (pharmacology) Antigens education Receptor Antigen-presenting cell Skin kinetics Skin education.field_of_study Computational model Chemistry Antigen uptake 020601 biomedical engineering Kinetics 030104 developmental biology Needles Immunology Pharmacokinetic model Biomedical engineering |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences European Journal of Pharmaceutical Sciences, 84, 18-25. Elsevier |
| ISSN: | 0928-0987 |
| Popis: | The skin is a promising location for vaccination with its abundant population ofantigen capturing and presenting cells. The development of new techniques, suchas the use of microneedles, can facilitate the delivery of vaccines into theskin. In recent years, many different types of microneedle arrays have beendesigned. However, their geometry and arrangement within an array may beoptimized to trigger sufficient antigen presenting cells. A computational modelcan support the rational design of microneedle arrays. Therefore, the aim of thecurrent study was to describe the distribution and kinetics of a deliveredantigen within the skin using a theoretical compartment model, which includedbinding of antigens to receptors and their uptake by cells, and to determinewhich parameters should be measured to validate the model for a specificapplication. Multiple simulations were performed using a high and low antigendelivery dose and a range of values for the rate constants. The resultsindicated 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. Thiswas caused by the difference in the ratio between the administered dose and theavailable binding sites and suggests the dose should be adapted to the number ofcells and receptors for a specific compound. The sensitivity analysis of themodel parameters confirmed that the initial dose and receptor concentrationswere indeed the two parameters that had the largest influence on the variance inantigen concentrations within the cells and circulation at equilibrium. Hence,these parameters are important to be measured in vivo. The presentedpharmacokinetics model can be used in future computational models to predict theinfluence of microneedle array geometry to optimize their design. |
| Databáze: | OpenAIRE |
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