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Diffusivity and structural polymorphism in some model stratum corneum lipid systems

R Lieckfeldt1, J Villalain, J C Gomez-Fernandez

  • 1Institute for Pharmaceutical Technology and Biopharmaceutics, Heidelberg University, Germany.

Biochimica Et Biophysica Acta
|August 15, 1993
PubMed
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Stratum corneum lipid mixtures form an L beta phase, crucial for drug diffusion barrier function. Ceramides and cholesterol are essential for maintaining this L beta phase structure.

Area of Science:

  • Biophysics
  • Materials Science
  • Dermatology

Background:

  • The stratum corneum (SC) acts as a primary barrier against water loss and environmental insults.
  • Understanding SC lipid structure and function is key to developing effective topical drug delivery systems.
  • Model lipid mixtures are used to investigate the biophysical properties of the SC barrier.

Purpose of the Study:

  • To investigate the influence of cholesterol, fatty acids, and ceramides on the polymorphism and drug diffusivity (Dlip) of model stratum corneum lipid mixtures.
  • To determine the structural basis for the barrier properties of SC lipid models.
  • To elucidate the roles of ceramides and cholesterol in maintaining SC lipid lamellar structures.

Main Methods:

  • Preparation of model stratum corneum lipid mixtures with varying compositions.

Related Experiment Videos

  • X-ray diffraction and Fourier transform infrared spectrometry to analyze lipid polymorphism.
  • Diffusional release models to determine the diffusivity of a model drug (Dlip).

    • Main Results:

    • An L beta phase structure was formed for lipid mixtures mimicking intact human SC composition.
    • Dlip was independent of water content (20-40% w/w) in the L beta phase, with bilayers exhibiting one-dimensional swelling.
    • Ceramides were essential for solubilizing cholesterol and enabling an L alpha-HII transition; cholesterol suppressed HII phase formation and ensured L beta structure.
    • Lipid mixtures with an L beta phase exhibited a diffusional barrier approximately one order of magnitude greater than unstructured mixtures.
    • HII structures were more permeable than L beta phases.

    Conclusions:

    • The L beta phase is the primary determinant of the diffusional barrier in model SC lipid mixtures.
    • Ceramides and cholesterol are critical for establishing and maintaining the L beta phase at physiological temperatures, ensuring barrier integrity.
    • While not directly influencing Dlip magnitude, ceramides and cholesterol are indispensable for the formation of a functional L beta barrier free of crystalline cholesterol and HII phases.