Related Experiment Videos
Animal models for transdermal drug delivery
R Panchagnula1, K Stemmer, W A Ritschel
1Division of Pharmaceutics and Drug Delivery Systems, University of Cincinnati Medical Center, OH, USA.
Summary
Snake skin shows the highest permeability for both water and 7-hydroxycoumarin. Skin permeability in rats and guinea pigs closely mimics human skin, with thickness influencing water but not 7-hydroxycoumarin permeation.
Area of Science:
- Dermal absorption and toxicology
- Comparative anatomy and physiology
- Pharmacokinetics and drug delivery
Background:
- Understanding interspecies differences in skin permeability is crucial for preclinical safety assessments and drug development.
- Previous studies have indicated variations in skin barrier function across species, impacting xenobiotic penetration.
- The lipophilicity and polarity of a compound significantly influence its dermal absorption pathway and rate.
Purpose of the Study:
- To compare the skin permeation characteristics of a polar compound (tritium-labeled water) and a nonpolar compound (14C-labeled 7-hydroxycoumarin) across 16 species.
- To evaluate the correlation between skin structural parameters (thickness, hair follicles) and compound permeability.
- To identify animal models with skin permeability profiles similar to human skin for predictive toxicology.
Main Methods:
- In vitro permeation studies using excised skin from 16 species, including human, Brattleboro rat, and hairless guinea pig.
- Quantification of tritium-labeled water and 14C-labeled 7-hydroxycoumarin permeation using liquid scintillation counting.
- Measurement of skin thickness (full, epidermal, stratum corneum) and hair follicle density per cm2 for each species.
Main Results:
- Snake skin demonstrated the highest permeability for both water and 7-hydroxycoumarin.
- Permeability and lag time values for water and 7-hydroxycoumarin across Brattleboro rat and hairless guinea pig skin were comparable to human skin.
- No correlation was found between hair follicle density and permeability for either compound; however, full skin thickness correlated with water permeability but not 7-hydroxycoumarin permeability.
Conclusions:
- Species-specific differences in skin structure significantly influence dermal absorption.
- Brattleboro rat and hairless guinea pig skin represent suitable models for predicting human skin permeability of both polar and nonpolar compounds.
- Skin thickness is a relevant factor for water permeation, while other unmeasured factors likely govern 7-hydroxycoumarin permeation across different species.