Mathematical modeling of transdermal delivery of topical drug formulations in a dynamic microfluidic diffusion chamber in health and disease

PLoS One. 2024 Apr 11;19(4):e0299501. doi: 10.1371/journal.pone.0299501. eCollection 2024.

Abstract

Mathematical models of epidermal and dermal transport are essential for optimization and development of products for percutaneous delivery both for local and systemic indication and for evaluation of dermal exposure to chemicals for assessing their toxicity. These models often help directly by providing information on the rate of drug penetration through the skin and thus on the dermal or systemic concentration of drugs which is the base of their pharmacological effect. The simulations are also helpful in analyzing experimental data, reducing the number of experiments and translating the in vitro investigations to an in-vivo setting. In this study skin penetration of topically administered caffeine cream was investigated in a skin-on-a-chip microfluidic diffusion chamber at room temperature and at 32°C. Also the transdermal penetration of caffeine in healthy and diseased conditions was compared in mouse skins from intact, psoriatic and allergic animals. In the last experimental setup dexamethasone, indomethacin, piroxicam and diclofenac were examined as a cream formulation for absorption across the dermal barrier. All the measured data were used for making mathematical simulation in a three-compartmental model. The calculated and measured results showed a good match, which findings indicate that our mathematical model might be applied for prediction of drug delivery through the skin under different circumstances and for various drugs in the novel, miniaturized diffusion chamber.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Caffeine* / pharmacology
  • Drug Compounding
  • Mice
  • Microfluidics
  • Models, Theoretical
  • Skin / metabolism
  • Skin Absorption*

Substances

  • Caffeine

Grants and funding

This work was supported by the TKP2021-EGA-42 grant, funded by the Ministry of Innovation and Technology, Hungary with support from the National Research Development and Innovation Fund (NRDIF) under the TKP2021 programme and also and by the ÚNKP-22-3 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development, and Innovation Fund. GSz acknowledges the support of the grant K145934 from NRDIF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.