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Nanotechnology In Vivo Characterizations

Nanotechnology In Vivo Characterizations. Pharmacokinetics (PK) Discussion: November 12, 2008. Use of Informatics to Expedite and Validate the Application of Nanotechnology in Biomedicine. Nanotechnology In Vivo Characterization Pharmacokinetics (PK) Meeting Agenda.

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Nanotechnology In Vivo Characterizations

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  1. Nanotechnology In Vivo Characterizations Pharmacokinetics (PK) Discussion: November 12, 2008 Use of Informatics to Expedite and Validate the Application of Nanotechnology in Biomedicine

  2. Nanotechnology In Vivo Characterization Pharmacokinetics (PK) Meeting Agenda

  3. DRAFT Nanotechnology In Vivo Characterization Model and Wireframes

  4. DRAFT In Vivo Characterization Model

  5. DRAFT In Vivo Pharmacokinetics Model AUC Bioavailability Clearance Half Life Volume of Distribution Tmax Cmax

  6. In Vivo Characterization - Pharmacokinetics

  7. In Vivo Characterization – Pharmacokinetics – Animal Model

  8. Pharmacokinetics - Treatment Information

  9. Pharmacokinetics - ADME Result

  10. DRAFT In Vivo PK Concepts

  11. Nanotechnology PK Questions

  12. Nanotechnology Pharmacokinetics (PK) Questions • What scientific questions related to Nanotechnology PK In Vivo Characterizations should we (and can we) focus on addressing? • What PK concepts are important to capture? • Are there specific files (spreadsheets, images, graphs) related to PK characterizations that should be uploaded or parsed for efficient data entry and searching? • What PK concepts are important to capture for interfacing with PK modeling and simulation systems in the future? • Of the identified concepts discussed during the meeting, which concepts should be included in a set of "minimal information" about a Nanotechnology In Vivo characterization? • Are there any Nanotechnology In Vivo Characterization data sets (or publications) available that we can leverage to validate our design going forward?

  13. 1. What scientific questions related to Nanotechnology PK In Vivo Characterizations should we (an can we) focus on addressing? • Try to monitor platform and drug – release from platform, track platform and drug, is it a stable? • Similar to liposomes • Can we engineer particles for optimal clearance? • Relevant within the platform charge, size effects distribution • Effects of clearance on size (cutoff points) • < 6 nm • > 6 nm • Difficult to generalize • Findings – ADME properties and general observations • Particle Deformability – AFM • Solid vs. liposome • Biliary clearance – Particles can enter bile through transcellular mechanism (au); difficult to measure unless measuring bile flow/output • Clearance type: Metabolic, renal excretion, billiary; RES uptake • Link to other characterizations

  14. 2. What PK concepts are important to capture? • DRAFT list of PK parameters: • AUC* (linear with respect to dose), Bioavailability* (Refers to oral administration; 99% of NP dosed IV; may still be bioavailability in IV route), Clearance* (includes clearance route), Half Life* (blood/plasma, whole body), Volume of Distribution*, Cmax*, Tmax*, C0 (Concentration at time 0) others? • Note: IV in animals may be different than IV in humans • Correlation of AUC with Clearance • AUC not linear, increase in exposure; results in toxicity; concern with NP formulations; saturation of RES; increase in exposure to patient; Model RES via surrogate cells. • Measure for particle deformability? – Check with chemists/material scientist • Estimate of size, filter, hydrodynamic diameter • Differs for particle type • Empirical studies • Clearance – time sampling of clearance (urinary clearance, renal clearance) • Clearance – Avg. clearance. Sometimes route not known • Filtration – Clearance rate approach rate of filtration (not as important) • Clearance • Hydrodynamic diameter and shape related • Modeling parameters - Deformability

  15. 3. Are there specific files (spreadsheets, images, graphs) related to PK characterizations that should be uploaded or parsed for efficient data entry and searching? • Example files: • Plasma vs. Time Graph, Tissue Distribution Spreadsheet, others? • JPEG, DICOM (MRI, Ultrasound, IR Fluorescent), DICOM extensions (annotations) • Plasma vs. Time Graph, Tissue Distribution – Spreadsheet format; parsing; save data entry time • Analysis Tools used to calculate PK parameters • WinNonLin, etc.

  16. Plasma vs. Time Plasma vs. Time Graphs PK Parameters

  17. Tissue Distribution

  18. 4. What PK concepts are important to capture for interfacing with PK modeling and simulation systems in the future? • Common used programs • WinNonLin – Pharsight; Compartimental and non-compartimental modeling • Concerned with non-compartimental modeling of data • Derives AUC, half-life clearance • Simple compartimental models – different administration routes • Program own models, DE can be used • Specific to profiles modeled • Physiological based PK models • acslXtreme – More for toxicology; scale between species; Look at blood flow, connect compartments using blood flow • Basic models – Rates of exchange Example PK Software: http://www.boomer.org/pkin/soft.html

  19. 5. Of the identified concepts discussed, which concepts should be included in a set of "minimal information" about a Nanotechnology In Vivo characterization?

  20. 6. Are there any Nanotechnology In Vivo Characterization data sets (or publications) available that we can leverage to validate our design going forward? • Wash U – In Vivo publication

  21. Closing and Next Steps

  22. Determine Monthly Meeting Date/Time Meeting “Heatmap”

  23. Monthly Topics • Discussion Forum • nano-invivo-char-l@list.nih.gov Thanks for Attending!

  24. Reference Links • NCL caNanoLab: http://cananolab.abcc.ncifcrf.gov/caNanoLab/ • caNanoLab Wiki site: https://wiki.nci.nih.gov/display/ICR/caNanoLab • caNanoLab Project site: http://gforge.nci.nih.gov/projects/calab • caNanoLab User’s Group: CANANOLAB-USERS-L@LIST.NIH.GOV • caBIG™ ICR Nano Working Group: http://gforge.nci.nih.gov/projects/nano/ • DRAFT In Vivo Characterization Materials: https://gforge.nci.nih.gov/docman/index.php?group_id=69&selected_doc_group_id=3982&language_id=1

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