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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 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential of Stratum Corneum Lipid Liposomes for Screening of Chemical Skin Penetration Enhancers

“…Fatty acids such as oleic acid was reported to disturb the packing of lipids and thereby increase the fluidity of lipids as well as form a permeable defect within the SC lipids. 27,28) Category B contained Span 40, 60, and 80, and sodium dodecyl sulfate. This group comprised mainly hydrophobic non-ionic surfactants (HLB 4-7) and anionic surfactants (HLB 40).…”

Effect of Penetration Enhancers on Transdermal Delivery of Propofol

“…Fatty acids such as OA and SA are seen to intercalate and disrupt the ordered lipid array and form separate fluid states that disorder endogenous lipids. 23,24) When the concentration of MEN, LIM and OA was increased the flux of PF was decreased. The optimum concentration of enhancers was observed.…”

Effect of Nerolidol and/or Levulinic Acid on the Thermotropic Behavior of Lipid Lamellar Structures in the Stratum Corneum

“…These enhancers act on intercellular lipid structures in the stratum corneum, reversibly decreasing its barrier function and increasing drug permeability. Many types of enhancers have been investigated, including alcohols, [1][2][3] pyrrolidones, 4,5) surfactants, 6,7) fatty acids, 8,9) and terpenes.10,11)The modes of action of penetration enhancers include increasing lipid partitioning or diffusion, disturbing lipid structure, and extracting lipids. 11) Chemical absorption enhancers must not only have high permeation effects but also a margin of safety for administration to live organisms, and thus many compounds are restricted from practical use.…”

“…These enhancers act on intercellular lipid structures in the stratum corneum, reversibly decreasing its barrier function and increasing drug permeability. Many types of enhancers have been investigated, including alcohols, [1][2][3] pyrrolidones, 4,5) surfactants, 6,7) fatty acids, 8,9) and terpenes.…”

“…11) Chemical absorption enhancers must not only have high permeation effects but also a margin of safety for administration to live organisms, and thus many compounds are restricted from practical use. Based on their safety and efficacy, terpenes [10][11][12] and fatty acids 8,9) have been studied extensively as permeation enhancers. Terpenes increase the diffusion of drugs in the intercellular lipids of the stratum corneum, and fatty acids increase the distribution of drugs to the surface.…”