Evaluation of nanoparticle interactions with skin
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EVALUATION OF NANOPARTICLE INTERACTIONS WITH SKIN. Nancy Ann Monteiro-Riviere, Ph.D. Professor of Investigative Dermatology and Toxicology Center for Chemical Toxicology Research and Pharmacokinetics North Carolina State University Raleigh, NC 27606. Overview.

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Evaluation of nanoparticle interactions with skin

EVALUATION OF NANOPARTICLE INTERACTIONS WITH SKIN

Nancy Ann Monteiro-Riviere, Ph.D.

Professor of Investigative Dermatology and Toxicology

Center for Chemical Toxicology Research and Pharmacokinetics

North Carolina State University

Raleigh, NC 27606


Overview
Overview

Focus of the proposed research is to assess the nature of interactions between manufactured nanoparticles and the skin.

  • Dermal absorption

  • Cutaneous toxicity

  • Distribution to skin after systemic exposure


Skin: PORTAL of entry and TARGET for toxicity

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  • Presently, there is minimal data available on the interaction of manufactured nanoparticles with the skin.

  • Decontamination would be significantly different than with “traditional” chemical exposure since solubilization or dilution might be less efficacious.

  • Basic requirement for a risk assessment includes information on hazard (e.g. toxicity) as well as exposure (e.g. absorption). This project should begin to define these boundaries.


Nanoparticles to be studied
Nanoparticles to be Studied interaction of manufactured nanoparticles with the skin.

  • Carbon Bucky balls and nanotubules

  • Iron oxide nanocrystals

  • Cadmium selenide nanocrystals

  • Eight particles types selected to study effect of size, shape and composition


Model systems
Model Systems interaction of manufactured nanoparticles with the skin.

  • Human epidermal keratinocyte cell culture

  • Porcine skin flow through diffusion cells

  • Isolated Perfused Porcine Skin Flap

    • Systemic uptake from perfusate

    • Assess absorption and toxicity of interesting particles


Experimental design
Experimental Design interaction of manufactured nanoparticles with the skin.

  • Nanoparticles will be applied topically in three exposure scenarios

    • Neat

    • Water

    • Mineral oil

  • Two Doses


Endpoints
Endpoints interaction of manufactured nanoparticles with the skin.

  • Light and Electron Microscopy

  • Cytotoxicity and IL-8 release

  • Particles that demonstrate potential toxicity or absorption in simpler models will then be studied in the IPPSF


KERATINOCYTE CYTOKINE NETWORK interaction of manufactured nanoparticles with the skin.


Isolated perfused porcine skin flap ippsf
Isolated Perfused Porcine Skin Flap (IPPSF) interaction of manufactured nanoparticles with the skin.

  • Isolated system with control over physiological parameters and perfusate composition

  • Intact functional microcirculation

  • Viable epidermis and dermis

  • Relatively large dosing area

  • Predictable extrapolation to in vivo

  • Allows for simultaneous assessment of absorption, skin disposition, pharmacokinetics and biomarkers of irritation

  • Humane alternative animal model

  • Cost-effective compared to in vivo studies


Ippsf surgery and perfusion systems
IPPSF Surgery and Perfusion Systems interaction of manufactured nanoparticles with the skin.


Ippsf closely parallels in vivo human absorption
IPPSF Closely Parallels interaction of manufactured nanoparticles with the skin.In Vivo Human Absorption


Conclusion
Conclusion interaction of manufactured nanoparticles with the skin.

  • Work should provide data on ability of a range of manufactured nanoparticles to interact with skin

  • Initial assessment of potential vehicle effects

  • Should provide boundaries for a dermal risk assessment on manufactured nanoparticle exposure


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