Preparation of a New Oligolamellar Stratum Corneum Lipid Model

Abstract

In this study, we present a preparation method for a new stratum corneum (SC) model system, which is closer to natural SC than the commonly used multilayer models. The complex setup of the native SC lipid matrix was mimicked by a ternary lipid mixture of ceramide [AP], cholesterol, and stearic acid. A spin coating procedure was applied to realize oligo-layered samples. The influence of lipid concentration, rotation speed, polyethylenimine, methanol content, cholesterol fraction, and annealing on the molecular arrangement of the new SC model was investigated by X-ray reflectivity measurements. The new oligo-SC model is closer to native SC in the total number of lipid membranes found between corneocytes. The reduction in thickness provides the opportunity to study the effects of drugs and/or hydrophilic penetration enhancers on the structure of SC in full detail by X-ray or neutron reflectivity. In addition, the oligo-lamellar systems allows one to infer not only the lamellar spacing, but also the total thickness of the oligo-SC model and changes thereof can be monitored. This improvement is most helpful for the understanding of transdermal drug administration on the nanoscale. The results are compared to the commonly used multilamellar lipid model systems and advantages and disadvantages of both models are discussed.

Phase Separation in Lipid Lamellae Result from Ceramide Conformations and Lateral Packing Structure

“…In interpreting the lamellar periodicity of Phase A, considering that the distance of all-trans C-C bonding is 0.127 nm, 31) the maximum chain length of α-hydroxy fatty acid is 2.29 nm. 19) The calculated length of the hairpin-shaped CER molecules 18,32) facing each other within a bilayer membrane has a lamellar period of about 4.6 nm, which is the length of the alkyl chains 19) and coincides with the lamellar period of Phase A.…”

“…9,10) Many studies were conducted to investigate the influence of lipid composition on hydrocarbon chain packing by mimicking the intercellular lipids of the human SC. [11][12][13][14][15][16][17][18][19][20] In this context, some groups reported that two different CER conformations formed in distinct phases of lamellar periodicity. [17][18][19][20] We previously reported that phases of different periodicity coexist in the N-(α-hydroxyoctadecanoyl)-dihydrosphingosine (CER[ADS]), CHOL, and palmitic acid (PA) complex model in which structural analysis was carried out using simultaneous small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction (WAXD) measurements at constant temperature.…”

“…2 H solid-state NMR spectroscopy, 17,18) neutron diffraction measurement, and X-ray diffraction measurement without temperature scanning, could not discriminate the differences in packing structure in phases with different lamellar periods. 14,[17][18][19] In order to determine the characteristics of hydrocarbon chain packing of each lamellar structure, we needed to conduct structural analysis using simultaneous SAXS and WAXD measurements.…”

Recent developments in the application of X-ray and neutron reflectivity to soft-matter systems

“…Such model systems are of obvious interest for many reasons, such as development of transdermal drug delivery systems to personal care products. Mueller and co-workers [47] have recently developed an improved preparation method for a new stratum corneum (SC) model system, which more closely resembles natural SC compared to the more commonly used multilayer models. Their new model is particularly geared towards exploitation by XRR or NR: a reduction in thickness provides the opportunity to study the effects of drugs and/or hydrophilic penetration enhancers on the structure of SC in full detail.…”

Interactions of NIPAM nanogels with model lipid multi-bilayers: A neutron reflectivity study

“…The silicon blocks were circular with a diameter of 100 mm and a thickness of 10 mm. In order to prepare the lipid multi-bilayers, the ceramide lipid or mixture of ceramide/ cholesterol/behenic acid (molar ratio [29] 1:0.3:1) were dissolved in chloroform to make a solution with the concentration of 2.5 mg/mL. Approximately 250 µL of the solution was pipetted onto the RCA [30] cleaned, hydrophilic pre-treated Si (1 1 1) substrate which was then spun at 1500 rmp for ∼15 s using a programmable spin coater until all of the chloroform was evaporated.…”