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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13.1      Bringing in-vivo considerations into NMS design
13.1.1    the in-vitro to ex-vivo to in-vivo paradigm In-vitro - importance of choosing suitable cell lines adding the complexity of in-vivo background while keeping the simplicity of in-vitro 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 In-vitro and ex-vivo are mostly “closed” systems, but not absolutely What is an “open” system? Attempts to isolate open systems
13.1.3    Layers of complexity of in-vivo systems Human cells in nude mice – a mixture of in-vitro and in-vivo “Model” small animal systems better model larger animal systems

13.2      Circulation time and biodistribution
13.2.1    factors affecting circulation time size/shape "stealth layer" coating zeta potential in-vivo in varying environments filtration and excretion dose/targeting
13.2.2    where do the NMS go in-vivo? checking the obvious organs (liver, spleen, kidney, blood…) finding NMS in tissues and organs
    within dissected tissue sections
    in blood (ex-vivo versus in-vivo flow cytometry)
    what is excreted?
13.2.3    Circulation time and dose optimization measure drug concentration over time 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 direct measurement of restoration of lost or compromised functions 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


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


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