Characterization of the Iontophoretic Permselective Properties of Human and Pig Skin

1
Characterization of the Iontophoretic
Permselective Properties of Human and Pig Skin

• D. Marro, M. B. Delgado-Charro and R. H. Guy
• Centre interuniversitaire de recherche et
  denseignement, Universities of Geneva and Lyon,
  Parc daffaires international, Archamps, France
• and
• University of Geneva, Section de Pharmacie,
  Geneva, Switzerland.

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Iontophoretic Transport Mechanisms
For a cationic drug Jionto JER JEO
Jpass Jpass 0 JER Electrorepulsive flux JEO
Electroosmotic flux
Anodal Chamber
Cathodal Chamber
Skin
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Iontophoretic Transport Mechanisms a)
Electrorepulsion
- Electrostatic interaction between the
applied electric field and the charged species in
the system. - Competition to transfer the
current drug and other ions present in the
formulation (Na). ? Size / Mobility ?
Relative concentration
EFFICIENCY OF DRUG TRANSPORT Fraction of total
applied current that is carried by the drug
across the skin.
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Iontophoretic Transport Mechanismsb)
Electroosmosis
_at_ pH 7.4 skin is ? cation permselective

• In vivo, this convective solvent flow
• Enhances transport of positively charged
  species.
• Allows the iontophoretic transport of neutral,
  hydrophilic species (glucose, mannitol).

• Coupled to ion transport
• Convective solvent flow
• Water
• Solutes
• (mainly anode-to-cathode)

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Objectives
1. To characterize the iontophoretic
permselective properties of Human Skin. 2. To
compare Human Skin to a model membrane widely
used in iontophoresis studies Porcine Ear Skin.
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Experimental Methods 1
- Manipulate in vitro the electrical charge of
the membrane (varying the pH of the bathing
solutions in the diffusion cell). - Quantify the
effect on electroosmosis (measuring the transport
of a hydrophilic non-electrolyte molecule
14C-Mannitol).
pH
Skin Charge
Permselectivity (Na vs. Cl-)
Electro- osmosis
Mannitol Transport
(Indept. var.)
(Expt. data)
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Experimental Methods 2
a) Anodal Flux - 14C-Mannitol in anodal
chamber - Cathode in receptor chamber
b) Cathodal Flux - 14C-Mannitol in cathodal
chamber - Anode in receptor chamber
e 14C-Mannitol
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Human Skin

6 h Iontophoretic fluxes n 3-7 s Statistical
diff. (plt0.05 Students t-test)
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Degree of Permselectivity (DP) Human Skin


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Pig Skin

6 h Iontophoretic fluxes n 5-9 s Statistical
diff. (plt0.05 Students t-test)
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Mannitol ElectrotransportHuman vs. Pig Skin
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Degree of Permselectivity Human vs. Pig Skin
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Isoelectric Point Human vs. Pig Skin
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Conclusions

• This work demonstrates that porcine skin is
  indeed a reasonable model for the human barrier
  in iontophoresis studies.
• The pI s of human and pig ear skin are very alike
  and are numerically close to that (4.5)
  previously reported for HMS.
• Thus, the general cation permselectivity of
  mammalian skin is confirmed.
• Certain observations require further elucidation
• Larger DP of porcine skin at 7.4
• Greater variability and higher electroosmotic
  flux in pig skin
• Sustained cathodal convective flow in this model
  at pH 5-6

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Acknowledgements

• We gratefully acknowledge financial support from
• Fonds national suisse de la recherche
  scientifique
• Program commun de recherche en génie biomédicale
  
• Universities of Geneva and Laussane
• Ecole Polytechnique Fédérale de Laussane
• University hospitals of the cantons of Geneva
  and Vaud

...and, thank-you for your attention!