Abstract by Liv Sofia Elinor Davies

Introduction
The outer layer of the human skin, the stratum corneum (SC), serves as the main barrier between the body and the external environment, protecting from pathogens and loss of water and nutrients. The only continuous path through the SC is the extracellular matrix (ECM), which is com-posed of equimolar ratios of ceramides (CERs), free fatty acids (FFAs), and cholesterol (CHOL) species. Reduction in the chain length of these lipids has been linked to a decrease in barrier integrity and is associated with disease, including atopic dermatitis (AD).

Aim
This study aims to develop methods for studying SC ECM lipid interactions with drugs and excipients in situ using neutron reflectometry (NR), ATR-FTIR spectroscopy, and diffusion cells. This is achieved in four parts. Part 1 covers the development and validation of the model setup. Part 2 focusses on the characterisation of SC ECM models of different lipid compositions and the selection of two compositions to mimic healthy and AD skin. Part 3 details the investigation of the interaction of propylene glycol (PG), a common excipient in pharmaceutical formulations for the skin, with the AD and healthy skin models.

Part 1-2
Lipid models of molar ratio 1:1:0.7 CER/FFA/CHOL were spin coated onto dimethylchlo-rooctylsilane (DOS) coated Si crystals. Using custom NR models and ATR-FTIR spectroscopy, the lamellar and lateral structures were analysed.

Part 3
The compositional/structural relationship was investigated with 9 SC ECM lipid models made from CER[AP] and/or [NP], palmitic (PA), stearic (SA), or lignoceric acid (LA), and CHOL. Varying the CER subtype had no effect on the lateral and lamellar structures at physiological temperatures. The FFA chain length however changed both, with PA leading to lower lateral tail density, and LA leading to higher, mimicking AD and healthy human SC ECM. Longer FFAs lead to thicker bilayers.

Part 4
Incubating CER[AP]/PA/CHOL (AP16) and CER[AP]/LA/CHOL (AP24) models with 20 % PG led to minimal increased lipid tail fluidisation in AP16. AP24 was more sensitive to the interac-tion, revealing lipid tail fluidisation and swelling of the headgroup layers. Investigating the effect of PG on salicylic acid (SA) diffusion revealed that PG doubled the SA diffusion in both models.

Conclusions and outlook
The studies show how to prepare simple SC ECM lipid models for study of drug/excipient effect on lateral and lamellar structures in situ and in drug diffusion experiments. Varying the lipid composition or drug formulations makes this a versatile tool to study a range of scenarios.