Investigation of ketoconazole diffusion into collodion membranes using step-scan FTIR-PAS technique

Results obtained from step-scan Fourier transform infrared photoacoustic spectroscopic (FTIR-PAS) experiments on ketoconazole diffusion into artificial dodecanol-collodion (DDC) membrane are presented. Measurements were performed for two frequencies of 13 Hz and 54 Hz at the spectral range ($500\div4500$) cm$^{-1}$. Both in-phase and quadrature components of photoacoustic signal were registered. Analysis of ketoconazole diffusion was carried out for 1512 cm$^{-1}$ line, whose intensity showed strong dependence on drug concentration. This analysis based on earlier proposed theoretical model of diffusion in a layered system. Experimental dependencies were fitted with theoretical curves using multiparameter fitting procedure. It allowed determination of the diffusion coefficient of ketoconazole in DDC membrane $D = (2.1\pm0.5)\cdot10^{-9}$ cm$^2$s$^{-1}$. Obtained results confirmed usability of step-scan FTIR-PAS techniques in investigations of diffusion processes

Evidence of free fatty acid interdigitation in stratum corneum model membranes based on ceramide [AP] by deuterium labelling.

This research paper provides direct evidence concerning the localisation of free fatty acids in stratum corneum lipid model membranes. We employed partially deuterated free fatty acids to gain further information about the assembly of a stratum corneum lipid model membrane based on a ceramide of the phytosphingosine type ceramide [AP] with particular respect to the position of the deuterated groups of the free fatty acids. The application of behenic 22,22,22 d 3 acid and cerotic 12,12,13,13 d 4 acid confirmed that the short chain ceramide [AP] forces the longer chained free fatty acids to incorporate into the bilayer created by ceramide [AP]. The ceramide [AP] molecules determine the structural assembly of this model membrane and obligate the long chain free fatty acids to either arrange inside this formation or to separate as a fatty acid rich phase

Investigation of a CER[NP] and [AP] Based Stratum Corneum Modeling Membrane System Using Specifically Deuterated CER Together with a Neutron Diffraction Approach

Neutron diffraction was used as a tool to investigate the lamellar as well as molecular nanostructure of ceramide [NP] ceramide [AP] cholesterol lignoceric acid model systems with a nativelike 2 1 ratio and a 1 2 ratio to study the influence of the ceramide [AP]. By using mixtures together with cholesterol and free fatty acids as well as a humidity and temperature chamber while measuring, natural conditions were simulated as closely as possible. Despite its simplicity, the system simulated the native stratum corneum lipid matrix fairly closely, showing a similar lamellar thickness with a repeat distance of 5.45 0.1 nm and a similar arrangement with overlapping long C24 chains. Furthermore, despite the very minor chemical difference between ceramide [NP] and ceramide [AP], which is only a single OH group, it was possible to demonstrate substantial differences between the structural influence of the two ceramides. Ceramide [AP] could be concluded to be arranged in such a way that its C24 chain in both ratios is somehow shorter than that of ceramide [NP], not overlapping as much with the opposite lamellar leaflet. Furthermore, in the unnatural 1 2 ratio, the higher ceramide [AP] content causes an increased tilt of the ceramide acyl chains. This leads to even less overlapping within the lamellar midplane, whereas the repeat distance stays the same as for the ceramide [NP] rich system. In this nativelike 2 1 ratio, the chains are arranged mostly straight, and the long C24 chains show a broad overlapping region in the lamellar midplan

Basic nanostructure of stratum corneum lipid matrices based on ceramides [EOS] and [AP] a neutron diffraction study

The goal of this study was to investigate the nanostructure of SC lipid model membranes comprising the most relevant SC lipids such as the unique structured omega acylceramide [EOS] in a near natural ratio with neutron diffraction. In models proposed recently the presence of ceramide [EOS] and FFA are necessary for the formation of one of the two existent crystalline lamellar phases of the SC lipids, the long periodicity phase as well as for the normal barrier function of the SC. The focus of this study was placed on the influence of the FFA BA on the membrane structure and its localization within the membrane based on the ceramides [EOS] and [AP]. The internal nanostructure of such membranes was obtained by Fourier synthesis from the experimental diffraction patterns. The resulting neutron scattering length density profiles showed that the exceptionally long ceramide [EOS] is arranged in a short periodicity phase created by ceramide [AP] by spanning through the whole bilayer and extending even further into the adjacent bilayer. Specifically deuterated BA allowed us to determine the exact position of this FFA inside this SC lipid model membrane. Furthermore, hydration experiments showed that the presented SC mimic system shows an extremely small intermembrane hydration of approximately 1 A, consequently the headgroups of the neighboring leaflets are positioned close to each othe

Synthesis of specifically deuterated ceramide [AP] C18 and its biophysical characterization using neutron diffraction

The very heterogeneous group of ceramides is known to be mandatory for proper barrier functions of the outermost layer of mammalian skin, referred to as stratum corneum SC . The synthesis of a specifically deuterated ceramide [AP] C18 variant is described. The synthesized ceramide contains the racemic forms of the a hydroxy fatty acid. For the biophysical implementation, the received diastereomeric ceramide was applied in a neutron diffraction experiment. Therefore, a SC lipid model membrane was prepared containing the described ceramide CER , cholesterol CHOL , stearic acid SA , and cholesterol sulfate ChS in a ratio of 55 25 15 5 wt . Thus, we were able to localize the deuterated molecule part within the bilayers. In the process, a short periodicity phase SPP was observed with a unit cell scale of about 44 . For the first time, we were able to confirm former ideas concerning the arrangement of the CER within this quaternary lipid model membran