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Related Experiment Video

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Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model
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A quantitative radioluminographic imaging method for evaluating lateral diffusion rates in skin.

Allison K Rush1, Matthew A Miller1, Edward D Smith2

  • 1James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45267, USA.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|August 5, 2015
PubMed
Summary
This summary is machine-generated.

A new method measures how compounds spread on skin using radiolabeled tracers. This helps understand topical bioavailability, especially for zinc pyrithione (ZnPT), showing faster lateral transport than transdermal permeation.

Keywords:
AntimicrobialCaffeine (PubChem CID:2519)DissolutionMolecular imagingPhosphorimagingStratum corneumTestosterone (PubChem CID:6013)Topical bioavailabilityZinc pyrithione (PubChem CID:26041)

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Area of Science:

  • Dermatology and Pharmaceutical Sciences
  • Radiochemistry and Imaging Techniques
  • Materials Science and Engineering

Background:

  • Understanding compound diffusion on skin is crucial for topical drug delivery and efficacy.
  • Lateral transport on the skin surface influences the bioavailability and performance of topical agents.
  • Zinc pyrithione (ZnPT) requires molecular-level access to microorganisms for its biocidal activity, necessitating efficient delivery.

Purpose of the Study:

  • To present and exemplify a novel method for quantifying lateral diffusion coefficients of exogenous compounds on excised skin.
  • To investigate the lateral transport kinetics of caffeine, testosterone, and zinc pyrithione (ZnPT) on skin.
  • To differentiate between diffusion-limited and dissolution rate-limited kinetics based on compound application levels.

Main Methods:

  • Sequential high-resolution imaging of β-radiation from [(14)C]-labeled compounds to map spatial distribution.
  • Application of radiolabeled test compounds (caffeine, testosterone, ZnPT) at varying concentrations on excised skin.
  • Analysis of concentration profile development to determine lateral diffusion coefficients.

Main Results:

  • Effective lateral diffusivities for caffeine and testosterone were measured as (1-4) × 10(-9) cm(2)/s and (3-9) × 10(-9) cm(2)/s, respectively.
  • ZnPT's lateral transport was formulation-dependent, showing effective diffusivities of (1-2) × 10(-9) cm(2)/s in water and (3-9) × 10(-9) cm(2)/s in a 1% body wash solution.
  • Lateral diffusivities were significantly higher (250-2000x) than estimated transverse diffusivities in the stratum corneum.

Conclusions:

  • Facile lateral transport on the skin surface is a key factor for the effective use of topical agents like ZnPT.
  • The developed imaging method accurately measures lateral diffusion coefficients, aiding in the assessment of topical bioavailability.
  • Formulation and molecular speciation significantly influence the lateral transport of compounds like ZnPT on the skin.