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

By James Leary

Biomedical Engineering, Purdue University, West Lafayette, IN

Published on

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," http://nanohub.org/resources/12495.

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Location

1083 BME, Purdue University, West Lafayette, IN

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