Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
NCSU CCTRPNCSU CCTRP
EVALUATION OFEVALUATION OF
NANOPARTICLE INTERACTIONSNANOPARTICLE INTERACTIONS
WITH SKINWITH SKIN
Nanc...
NCSU CCTRPNCSU CCTRP
OverviewOverview
Focus of the proposed research is toFocus of the proposed research is to
assess the ...
NCSU CCTRPNCSU CCTRP
SkinSkin: PORTAL of entry: PORTAL of entry andand TARGET for toxicityTARGET for toxicity
{
NCSU CCTRPNCSU CCTRP
Human SkinHuman Skin
NCSU CCTRPNCSU CCTRP
Porcine SkinPorcine Skin
NCSU CCTRPNCSU CCTRP
Presently, there is minimal data available on thePresently, there is minimal data available on the
in...
NCSU CCTRPNCSU CCTRP
Nanoparticles to be StudiedNanoparticles to be Studied
Carbon Bucky balls and nanotubulesCarbon Bucky...
NCSU CCTRPNCSU CCTRP
Model SystemsModel Systems
Human epidermal keratinocyte cellHuman epidermal keratinocyte cell
culture...
NCSU CCTRPNCSU CCTRP
Experimental DesignExperimental Design
Nanoparticles will be applied topicallyNanoparticles will be a...
NCSU CCTRPNCSU CCTRP
EndpointsEndpoints
Light and Electron MicroscopyLight and Electron Microscopy
Cytotoxicity and IL-8 r...
NCSU CCTRPNCSU CCTRP
NCSU CCTRPNCSU CCTRP
KERATINOCYTE CYTOKINE NETWORKKERATINOCYTE CYTOKINE NETWORK
NCSU CCTRPNCSU CCTRP
NCSU CCTRPNCSU CCTRP
Isolated Perfused Porcine Skin Flap (IPPSF)Isolated Perfused Porcine Skin Flap (IPPSF)
Isolated syste...
NCSU CCTRPNCSU CCTRP
IPPSF Surgery and Perfusion SystemsIPPSF Surgery and Perfusion Systems
NCSU CCTRPNCSU CCTRP
IPPSF Closely ParallelsIPPSF Closely Parallels In VivoIn Vivo Human AbsorptionHuman Absorption
IPPSF ...
NCSU CCTRPNCSU CCTRP
ConclusionConclusion
Work should provide data on ability ofWork should provide data on ability of
a r...
Upcoming SlideShare
Loading in …5
×

MS PowerPoint

354 views

Published on

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

MS PowerPoint

  1. 1. NCSU CCTRPNCSU CCTRP EVALUATION OFEVALUATION OF NANOPARTICLE INTERACTIONSNANOPARTICLE INTERACTIONS WITH SKINWITH SKIN Nancy Ann Monteiro-Riviere, Ph.D.Nancy Ann Monteiro-Riviere, Ph.D. Professor of Investigative Dermatology andProfessor of Investigative Dermatology and ToxicologyToxicology Center for Chemical Toxicology Research andCenter for Chemical Toxicology Research and PharmacokineticsPharmacokinetics North Carolina State UniversityNorth Carolina State University Raleigh, NC 27606Raleigh, NC 27606
  2. 2. NCSU CCTRPNCSU CCTRP OverviewOverview Focus of the proposed research is toFocus of the proposed research is to assess the nature of interactionsassess the nature of interactions between manufactured nanoparticlesbetween manufactured nanoparticles and the skin.and the skin. Dermal absorptionDermal absorption Cutaneous toxicityCutaneous toxicity Distribution to skin after systemicDistribution to skin after systemic exposureexposure
  3. 3. NCSU CCTRPNCSU CCTRP SkinSkin: PORTAL of entry: PORTAL of entry andand TARGET for toxicityTARGET for toxicity {
  4. 4. NCSU CCTRPNCSU CCTRP Human SkinHuman Skin
  5. 5. NCSU CCTRPNCSU CCTRP Porcine SkinPorcine Skin
  6. 6. NCSU CCTRPNCSU CCTRP Presently, there is minimal data available on thePresently, there is minimal data available on the interaction of manufactured nanoparticles withinteraction of manufactured nanoparticles with the skin.the skin. Decontamination would be significantlyDecontamination would be significantly different than with “traditional” chemicaldifferent than with “traditional” chemical exposure since solubilization or dilution mightexposure since solubilization or dilution might be less efficacious.be less efficacious. Basic requirement for a risk assessmentBasic requirement for a risk assessment includes information on hazard (e.g. toxicity) asincludes information on hazard (e.g. toxicity) as well as exposure (e.g. absorption). This projectwell as exposure (e.g. absorption). This project should begin to define these boundaries.should begin to define these boundaries.
  7. 7. NCSU CCTRPNCSU CCTRP Nanoparticles to be StudiedNanoparticles to be Studied Carbon Bucky balls and nanotubulesCarbon Bucky balls and nanotubules Iron oxide nanocrystalsIron oxide nanocrystals Cadmium selenide nanocrystalsCadmium selenide nanocrystals Eight particles types selected to studyEight particles types selected to study effect of size, shape and compositioneffect of size, shape and composition
  8. 8. NCSU CCTRPNCSU CCTRP Model SystemsModel Systems Human epidermal keratinocyte cellHuman epidermal keratinocyte cell cultureculture Porcine skin flow through diffusionPorcine skin flow through diffusion cellscells Isolated Perfused Porcine Skin FlapIsolated Perfused Porcine Skin Flap  Systemic uptake from perfusateSystemic uptake from perfusate  Assess absorption and toxicity ofAssess absorption and toxicity of interesting particlesinteresting particles
  9. 9. NCSU CCTRPNCSU CCTRP Experimental DesignExperimental Design Nanoparticles will be applied topicallyNanoparticles will be applied topically in three exposure scenariosin three exposure scenarios  NeatNeat  WaterWater  Mineral oilMineral oil  Two DosesTwo Doses
  10. 10. NCSU CCTRPNCSU CCTRP EndpointsEndpoints Light and Electron MicroscopyLight and Electron Microscopy Cytotoxicity and IL-8 releaseCytotoxicity and IL-8 release Particles that demonstrate potentialParticles that demonstrate potential toxicity or absorption in simplertoxicity or absorption in simpler models will then be studied in themodels will then be studied in the IPPSFIPPSF
  11. 11. NCSU CCTRPNCSU CCTRP
  12. 12. NCSU CCTRPNCSU CCTRP KERATINOCYTE CYTOKINE NETWORKKERATINOCYTE CYTOKINE NETWORK
  13. 13. NCSU CCTRPNCSU CCTRP
  14. 14. NCSU CCTRPNCSU CCTRP Isolated Perfused Porcine Skin Flap (IPPSF)Isolated Perfused Porcine Skin Flap (IPPSF) Isolated system with control over physiologicalIsolated system with control over physiological parameters and perfusate compositionparameters and perfusate composition Intact functional microcirculationIntact functional microcirculation Viable epidermis and dermisViable epidermis and dermis Relatively large dosing areaRelatively large dosing area Predictable extrapolation toPredictable extrapolation to in vivoin vivo Allows for simultaneous assessment of absorption,Allows for simultaneous assessment of absorption, skin disposition, pharmacokinetics and biomarkersskin disposition, pharmacokinetics and biomarkers of irritationof irritation Humane alternative animal modelHumane alternative animal model Cost-effective compared toCost-effective compared to in vivoin vivo studiesstudies
  15. 15. NCSU CCTRPNCSU CCTRP IPPSF Surgery and Perfusion SystemsIPPSF Surgery and Perfusion Systems
  16. 16. NCSU CCTRPNCSU CCTRP IPPSF Closely ParallelsIPPSF Closely Parallels In VivoIn Vivo Human AbsorptionHuman Absorption IPPSF vs In Vivo Human R 2 = 0.91 0 5 10 15 20 25 30 35 0 5 10 15 20 25 30 35 40 IPPSF (% Dose) InVivoHuman(%Dose)
  17. 17. NCSU CCTRPNCSU CCTRP ConclusionConclusion Work should provide data on ability ofWork should provide data on ability of a range of manufactured nanoparticlesa range of manufactured nanoparticles to interact with skinto interact with skin Initial assessment of potential vehicleInitial assessment of potential vehicle effectseffects Should provide boundaries for aShould provide boundaries for a dermal risk assessment ondermal risk assessment on manufactured nanoparticle exposuremanufactured nanoparticle exposure

×