BME 695L Lecture 13: Designing Nanomedical Systems (NMS) for In-vivo Use

By James Leary

Biomedical Engineering, Purdue University, West Lafayette, IN

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Abstract

See references below for related reading.

13.1      Bringing in-vivo considerations into NMS design
13.1.1    the in-vitro to ex-vivo to in-vivo paradigm
         13.1.1.1 In-vitro - importance of choosing suitable cell lines
         13.1.1.2 adding the complexity of in-vivo background while keeping the simplicity of in-vitro
         13.1.1.3 all the complexity of ex-vivo plus the “active” components of a real animal
13.1.2    In-vivo systems are open, “active” systems with multiple layers of complexity
         13.1.2.1 In-vitro and ex-vivo are mostly “closed” systems, but not absolutely
         13.1.2.2 What is an “open” system?
         13.1.2.3 Attempts to isolate open systems
13.1.3    Layers of complexity of in-vivo systems
         13.1.3.1 Human cells in nude mice – a mixture of in-vitro and in-vivo
         13.1.3.2 “Model” small animal systems
         13.1.3.3 better model larger animal systems

13.2      Circulation time and biodistribution
13.2.1    factors affecting circulation time
         13.2.1.1 size/shape
         13.2.1.2 "stealth layer" coating
         13.2.1.3 zeta potential in-vivo in varying environments
         13.2.1.4 filtration and excretion
         13.2.1.5 dose/targeting
13.2.2    where do the NMS go in-vivo?
         13.2.2.1 checking the obvious organs (liver, spleen, kidney, blood…)
         13.2.2.2 finding NMS in tissues and organs
             13.2.2.2.1 in-vivo
             13.2.2.2.2 within dissected tissue sections
             13.2.2.2.3 in blood (ex-vivo versus in-vivo flow cytometry)
             13.2.2.2.4 what is excreted?
13.2.3    Circulation time and dose optimization
         13.2.3.1 measure drug concentration over time
         13.2.3.2 is there an optimal drug dose?

13.4      In-vivo targeting and mistargeting
13.4.1    mode of administration (intravenous, oral, intra-tumor…)
13.4.2    how can we assess targeting in-vivo? (MRI, fluorescence, …)
13.4.3    a rare-cell targeting problem
13.4.4    consequences of mistargeting
13.4.5    balancing dosing, therapeutic efficacy, and consequences of mistargeting

13.5      Evaluating therapeutic efficacy in-vivo
13.5.1    advantages of non-invasive measurements
13.5.2    measures of tumor load/shrinkage (tumor size, weight,..)
13.5.3    other measures of disease effects
         13.5.3.1 direct measurement of restoration of lost or compromised functions
         13.5.3.2 indirect measures of disease effects (e.g. behavior, weight gain/loss, .)
13.5.4    Some examples of in-vivo work with NMS

13.6      Summary
13.6.1    Choosing an appropriate animal model and getting it approved takes time!
13.6.2    Animal experiments are expensive and time-consuming
13.6.3    Performing in-vivo measurements of drug delivery and therapeutic efficacy are more challenging and expensive than in-vitro or ex-vivo work!
13.6.4    But ultimately you must show that the NMS works in-vivo

Credits

Copyright © 2011, James F. Leary, All rights reserved.

References

Bhirde, A.A., Patel, V., Gavard, J., Zhang, G., Sousa, A.A., Masedunskas, A., Leapman, R.D., Weigert, R., Gutkind, J.S., Rusling, J.F. "Targeted Killing of Cancer Cells in Vivo and in Vitro with EGF-Directed Carbon Nanotube-Based Drug Delivery". ACS Nano 3(2) 307-316 (2009).
Cartier, R., Kaufner, L., Paulke, B.R., Wustneck, R., Pietschmann, S., Michel, R., Bruhn, H., Pison, U. "Latex nanoparticles for multimodal imaging and detection in vivo". Nanotechnology 18:195102 – 195113 (2007).
Chenga, J., Teply, B.A., Sherifia, I., Sunga, J., Luthera, G., Gua, F.X., Levy-Nissenbauma, E., Radovic-Morenob, A.F., Langer, R., Farokhzad, O.C. "Formulation of functionalized PLGA–PEG nanoparticles for in vivo targeted drug delivery". Biomaterials 28: 869–876 (2007). (Full text available at nih.gov)
Farokhzad, O.C., Cheng, J., Teply, B.A., Sherifi, I., Jon, S., Kantoff, P.W., Richie, J.P., Langer, R. "Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo". PNAS 103(6): 6313–6320 (2006).
Hou, C-H, Hou, S-M, Hsueh, Y-S, Lin, J., Wu, H-C, Lin, F-H "The in vivo performance of biomagnetic hydroxyapatite nanoparticles in cancer hyperthermia therapy". Biomaterials 30: 3956–3960 (2009). (Full text available at nih.gov)

Cite this work

Researchers should cite this work as follows:

  • James Leary (2011), "BME 695L Lecture 13: Designing Nanomedical Systems (NMS) for In-vivo Use," https://nanohub.org/resources/12495.

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Location

1083 BME, Purdue University, West Lafayette, IN

Tags

BME 695L Lecture 13: Designing Nanomedical Systems (NMS) for In-vivo Use
  • ECE 695L Lecture 13: Designing nanodelivery systems for in-vivo use 1. ECE 695L Lecture 13: Designing… 8.6333333333333329
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  • 13.1 Bringing in-vivo considerations into NMS design 2. 13.1 Bringing in-vivo consider… 18.233333333333334
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  • 13.1 Bringing in-vivo considerations into NMS design (continued) 3. 13.1 Bringing in-vivo consider… 238.7
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  • 13.1 Bringing in-vivo considerations into NMS design (continued) 4. 13.1 Bringing in-vivo consider… 449
    00:00/00:00
  • 13.2 Circulation time and biodistribution 5. 13.2 Circulation time and biod… 750.16666666666663
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  • 13.2 Circulation time and biodistribution (continued) 6. 13.2 Circulation time and biod… 1284.7666666666667
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  • Near Infrared Fluorescence (NIRF) Imaging 7. Near Infrared Fluorescence (NI… 1431.5
    00:00/00:00
  • Ex vivo results of HGC-Cy5.5-SPIOs 8. Ex vivo results of HGC-Cy5.5-S… 1680.7333333333334
    00:00/00:00
  • Problem: How to find 9. Problem: How to find "suboptic… 1815.4666666666667
    00:00/00:00
  • Labeled PCR products (amplicons) form an optically sized diameter of detectable (by scanning image cytometry) signal around each nanoparticle 10. Labeled PCR products (amplicon… 1900.2333333333334
    00:00/00:00
  • DNA barcode in-situ PCR-amplified nanoparticle signals enable rapid detection of small numbers of nanoparticles over large areas in tissues 11. DNA barcode in-situ PCR-amplif… 1920.8333333333333
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  • In-vivo distributions of nanoparticles 12. In-vivo distributions of nanop… 1959.8666666666666
    00:00/00:00
  • In-vivo biodistribution of radiolabeled nanoparticles 13. In-vivo biodistribution of rad… 1990.2
    00:00/00:00
  • Interaction of rhodamine B-labelled EPMA nanoparticles with blood components using flow cytometry 14. Interaction of rhodamine B-lab… 2109.8
    00:00/00:00
  • Use of Ultra-High Speed Flow Cytometry and Cell Sorting to Select Targeting Aptamers and to Evaluate Targeting to Rare Cells for Nanomedicine 15. Use of Ultra-High Speed Flow C… 2245.8333333333335
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  • 15.2 Circulation time and biodistribution (continued) 16. 15.2 Circulation time and biod… 2319.5666666666666
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  • 13.4 In-vivo targeting and mistargeting 17. 13.4 In-vivo targeting and mis… 2468.5666666666666
    00:00/00:00
  • Tools for Evaluating Targeting 18. Tools for Evaluating Targeting 2938.2333333333331
    00:00/00:00
  • Imaging Systems 19. Imaging Systems 2973.3666666666668
    00:00/00:00
  • Molecular Imaging Modalities 20. Molecular Imaging Modalities 3050.6666666666665
    00:00/00:00
  • Near Infrared Fluorescence (NIRF) Imaging 21. Near Infrared Fluorescence (NI… 3081.0666666666666
    00:00/00:00
  • Combination Technology with MR, NIRF, and Confocal Images 22. Combination Technology with MR… 3091.9
    00:00/00:00
  • Carbon nanotubes for drug delivery in-vivo 23. Carbon nanotubes for drug deli… 3113.3666666666668
    00:00/00:00
  • Cellular internalization and selective uptake of carbon nanotubes 24. Cellular internalization and s… 3187.2
    00:00/00:00
  • Detection of nanotube bioconjugates in tumors in vivo 25. Detection of nanotube bioconju… 3432.6666666666665
    00:00/00:00
  • Analysis of the distribution of nanotube bioconjugates in vivo 26. Analysis of the distribution o… 3465.1
    00:00/00:00
  • 13.5 Evaluating therapeutic efficacy in-vivo 27. 13.5 Evaluating therapeutic ef… 3493.3666666666668
    00:00/00:00
  • Combination Technology with MR, NIRF, and Confocal Images 28. Combination Technology with MR… 3635.3
    00:00/00:00
  • In vivo results of HGC-Cy5.5-SPIOs 29. In vivo results of HGC-Cy5.5-S… 3643.3666666666668
    00:00/00:00
  • Selective killing of cancer cells using SWNT bioconjugates 30. Selective killing of cancer ce… 3700.9333333333334
    00:00/00:00
  • Development of Docetaxel-encapsulated pegylated PLGA NP-Apt bioconjugates 31. Development of Docetaxel-encap… 3730.9333333333334
    00:00/00:00
  • Comparative efficacy of treatments for human prostate cancer in nude mice 32. Comparative efficacy of treatm… 3788.1666666666665
    00:00/00:00
  • Hyperthermic destruction of peri-tumor insertion of biomagnetic hydroxyapatite nanoparticles 33. Hyperthermic destruction of pe… 3859.2666666666669
    00:00/00:00
  • 13.6 Summary 34. 13.6 Summary 3978.3333333333335
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  • References 35. References 4128.666666666667
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