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In vitro visualization and quantification of oleic acid induced changes in transdermal transport using two-photon
1Departments of Chemical Engineering and Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
The Journal of Investigative Dermatology
|July 10, 2001
Summary
Two-photon microscopy visualized how oleic acid alters skin barrier function. This technique quantified changes in probe distribution, revealing mechanisms of enhanced transdermal transport for hydrophilic and hydrophobic molecules.
Area of Science:
- Dermatology
- Biophysics
- Materials Science
Background:
- The stratum corneum acts as a primary barrier to transdermal drug delivery.
- Understanding the mechanisms of skin penetration enhancers is crucial for optimizing drug delivery.
- Two-photon scanning fluorescence microscopy offers high-resolution 3D imaging of molecular distributions within tissues.
Purpose of the Study:
- To visualize and quantify the 3D spatial distribution of hydrophilic and hydrophobic fluorescent probes in human skin.
- To investigate the effects of oleic acid, a known penetration enhancer, on transdermal transport properties.
- To elucidate the mechanistic changes in skin barrier function induced by oleic acid.
Main Methods:
- Utilized two-photon scanning fluorescence microscopy to image sulforhodamine B (hydrophilic) and rhodamine B hexyl ester (hydrophobic) in human cadaver skin.
- Quantified probe distributions and calculated changes in concentration gradients and partition coefficients.
- Applied mathematical models of transdermal transport to determine alterations in diffusion coefficients and barrier diffusion lengths.
Main Results:
- Both probes localized within the lipid multilamellae of the stratum corneum.
- Oleic acid increased the vehicle to skin partition coefficient for both probes.
- The hydrophobic probe's enhanced permeability was mainly due to increased partition coefficient, while the hydrophilic probe showed increased partition coefficient and diffusion coefficient.
Conclusions:
- Two-photon microscopy provides detailed 3D visualization of probe distribution in skin.
- Quantification of these distributions offers mechanistic insights into transdermal transport.
- Oleic acid alters skin barrier properties by affecting both probe partitioning and diffusion, with differential effects on hydrophilic and hydrophobic molecules.
