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Title: Evidence that oleic acid exists in a separate phase within stratum corneum lipids

Abstract

Oleic acid is known to be a penetration enhancer for polar to moderately polar molecules. A mechanism related to lipid phase separation has been previously proposed by this laboratory to explain the increases in skin transport. In the studies presented here, Fourier transform infrared spectroscopy (FT-IR) was utilized to investigate whether or not oleic acid exists in a separate phase within stratum corneum (SC) lipids. Per-deuterated oleic acid was employed allowing the conformational phase behavior of the exogenously added fatty acid and the endogenous SC lipids to be monitored independently of each other. The results indicated that oleic acid exerts a significant effect on the SC lipids, lowering the lipid transition temperature (Tm) in addition to increasing the conformational freedom or flexibility of the endogenous lipid alkyl chains above their Tm. At temperatures lower than Tm, however, oleic acid did not significantly change the chain disorder of the SC lipids. Similar results were obtained with lipids isolated from the SC by chloroform:methanol extraction. Oleic acid, itself, was almost fully disordered at temperatures both above and below the endogenous lipid Tm in the intact SC and extracted lipid samples. This finding suggested that oleic acid does exist as a liquid withinmore » the SC lipids. The coexistence of fluid oleic acid and ordered SC lipids, at physiological temperatures, is consistent with the previously proposed phase-separation transport mechanism for enhanced diffusion.« less

Authors:
; ; ;  [1]
  1. (Central Research Division, Pfizer Inc., Groton, CT (USA))
Publication Date:
OSTI Identifier:
5398374
Resource Type:
Journal Article
Resource Relation:
Journal Name: Pharmaceutical Research; (United States); Journal Volume: 8:3
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; LIPIDS; MOLECULAR STRUCTURE; OLEIC ACID; STRUCTURE-ACTIVITY RELATIONSHIPS; DEUTERIUM; EPIDERMIS; FOURIER TRANSFORMATION; INFRARED SPECTRA; NUCLEAR MAGNETIC RESONANCE; SWINE; THERMODYNAMICS; TRACER TECHNIQUES; ANIMAL TISSUES; ANIMALS; BODY; CARBOXYLIC ACIDS; DOMESTIC ANIMALS; EPITHELIUM; HYDROGEN ISOTOPES; INTEGRAL TRANSFORMATIONS; ISOTOPE APPLICATIONS; ISOTOPES; LIGHT NUCLEI; MAGNETIC RESONANCE; MAMMALS; MONOCARBOXYLIC ACIDS; NUCLEI; ODD-ODD NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; RESONANCE; SKIN; SPECTRA; STABLE ISOTOPES; TISSUES; TRANSFORMATIONS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Ongpipattanakul, B., Burnette, R.R., Potts, R.O., and Francoeur, M.L. Evidence that oleic acid exists in a separate phase within stratum corneum lipids. United States: N. p., 1991. Web. doi:10.1023/A:1015845632280.
Ongpipattanakul, B., Burnette, R.R., Potts, R.O., & Francoeur, M.L. Evidence that oleic acid exists in a separate phase within stratum corneum lipids. United States. doi:10.1023/A:1015845632280.
Ongpipattanakul, B., Burnette, R.R., Potts, R.O., and Francoeur, M.L. 1991. "Evidence that oleic acid exists in a separate phase within stratum corneum lipids". United States. doi:10.1023/A:1015845632280.
@article{osti_5398374,
title = {Evidence that oleic acid exists in a separate phase within stratum corneum lipids},
author = {Ongpipattanakul, B. and Burnette, R.R. and Potts, R.O. and Francoeur, M.L.},
abstractNote = {Oleic acid is known to be a penetration enhancer for polar to moderately polar molecules. A mechanism related to lipid phase separation has been previously proposed by this laboratory to explain the increases in skin transport. In the studies presented here, Fourier transform infrared spectroscopy (FT-IR) was utilized to investigate whether or not oleic acid exists in a separate phase within stratum corneum (SC) lipids. Per-deuterated oleic acid was employed allowing the conformational phase behavior of the exogenously added fatty acid and the endogenous SC lipids to be monitored independently of each other. The results indicated that oleic acid exerts a significant effect on the SC lipids, lowering the lipid transition temperature (Tm) in addition to increasing the conformational freedom or flexibility of the endogenous lipid alkyl chains above their Tm. At temperatures lower than Tm, however, oleic acid did not significantly change the chain disorder of the SC lipids. Similar results were obtained with lipids isolated from the SC by chloroform:methanol extraction. Oleic acid, itself, was almost fully disordered at temperatures both above and below the endogenous lipid Tm in the intact SC and extracted lipid samples. This finding suggested that oleic acid does exist as a liquid within the SC lipids. The coexistence of fluid oleic acid and ordered SC lipids, at physiological temperatures, is consistent with the previously proposed phase-separation transport mechanism for enhanced diffusion.},
doi = {10.1023/A:1015845632280},
journal = {Pharmaceutical Research; (United States)},
number = ,
volume = 8:3,
place = {United States},
year = 1991,
month = 3
}
  • The stratum corneum is the uppermost layer of the skin and acts as a barrier to keep out contaminants and retain moisture. Understanding the molecular structure and behavior of this layer will provide guidance for optimizing its biological function. In this study we use a model mixture comprised of equimolar portions of ceramide NS (24:0), lignoceric acid, and cholesterol to model the effect of the addition of small amounts of oleic acid to the bilayer at 300 and 340 K. Five systems at each temperature have been simulated with concentrations between 0 and 0.1 mol % oleic acid. Our majormore » finding is that subdiffusive behavior over the 200 ns time scale is evident in systems at 340 K, with cholesterol diffusion being enhanced with increased oleic acid. Importantly, cholesterol and other species diffuse faster when radial densities indicate nearest neighbors include more cholesterol. We also find that, with the addition of oleic acid, the bilayer midplane and interfacial densities are reduced and there is a 3% decrease in total thickness occurring mostly near the hydrophilic interface at 300 K with reduced overall density at 340 K. Increased interdigitation occurs independent of oleic acid with a temperature increase. Slight ordering of the long non-hydroxy fatty acid of the ceramide occurs near the hydrophilic interface as a function of the oleic acid concentration, but no significant impact on hydrogen bonding is seen in the chosen oleic acid concentrations.« less
  • Irradiation with suberythemal doses of either UV-A or UV-B yielded an increase in the amount of stratum corneum lipids extracted from the lumbar skin area of 20 volunteers. These lipids were quantified after separation by high-performance thin-layer chromatography. Ten subfractions in the ceramide region were separated; two of them (fractions 7a and 7b) were only detectable after UV-A or UV-B irradiation. Improvement of barrier function after UV irradiation of human skin with suberythemal doses may be related to an increase in the stratum corneum ceramides.
  • In a recent investigation we showed that murine keratinocyte cultures grown at the air/medium interface in the presence of dermis exhibit morphologic differentiation comparable to that seen in vivo, including the formation of lamellar granules and stratum corneum intercellular lipid lamellae. In the present study, lifted cultures were found to more closely reproduce the lipid composition of the parent epidermal tissue than submerged cultures grown on plastic. In addition, the specific fatty acid profile of individual lipid classes in lifted cultures was, in general, remarkably well maintained in vitro. Acylceramides, which are highly enriched in linoleic acid in vivo, remainedmore » enriched in vitro; however, the linoleic acid content of the cultures was substantially lower than that in vivo, confirming previous reports of the relative essential fatty acid deficiency of standard culture media. As the lifted cultures differentiated over time, the lipid composition changed to reflect the formation of a stratum corneum with its different complement of lipids. Label from (U-/sup 14/C)linoleic acid was specifically incorporated into linoleate-containing lipids during short pulses in both submerged and lifted cultures. Changes in label distribution over a long chase period in lifted cultures indicated that linoleate was transferred from phospholipids to ceramides, providing evidence for the ''recycling'' of essential fatty acids in epidermis.« less
  • Noninvasive delivery of macromolecules across intact skin is challenging but would allow for needle-free administration of many pharmaceuticals. Biphasic vesicles, a novel lipid-based topical delivery system, have been shown to deliver macromolecules into the skin. Investigation of the delivery mechanism of interferon alpha (IFN {alpha}), as a model protein, by biphasic vesicles could improve understanding of molecular transport through the stratum corneum and allow for the design of more effective delivery systems. The interaction of biphasic vesicles with human skin and isolated stratum corneum membrane was investigated by confocal microscopy, differential scanning calorimetry (DSC) and small- and wide-angle X-ray scatteringmore » (SAXS and WAXS). Confocal microscopy revealed that biphasic vesicles delivered IFN {alpha} intercellularly, to a depth of 70 {micro}m, well below the stratum corneum and into the viable epidermis. DSC and SAXS/WAXS data suggest that the interaction of biphasic vesicles with SC lipids resulted in the formation of a three-dimensional cubic Pn3m polymorphic phase by the molecular rearrangement of intercellular lipids. This cubic phase could be an intercellular permeation nanopathway that may explain the increased delivery of IFN {alpha} by biphasic vesicles. Liposomes and submicrometer emulsion (the individual building blocks of biphasic vesicles) separately and methylcellulose gel, an alternative topical vehicle, did not induce a cubic phase and delivered low amounts of IFN {alpha} below the stratum corneum. Molecular modeling of the cubic Pn3m phase and lamellar-to-cubic phase transitions provides a plausible mechanism for transport of IFN {alpha}. It is hypothesized that induction of a Pn3m cubic phase in stratum corneum lipids could make dermal and transdermal delivery of other macromolecules also possible.« less