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

See references below for related reading.13.1      Bringing in-vivo considerations into NMS design13.1.1    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 animal13.1.2    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 systems13.1.3    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 systems13.2      Circulation time and biodistribution13.2.1    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/targeting13.2.2    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 mistargeting13.4.1    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 problem13.4.4    consequences of mistargeting13.4.5    balancing dosing, therapeutic efficacy, and consequences of mistargeting13.5      Evaluating therapeutic efficacy in-vivo13.5.1    advantages of non-invasive measurements13.5.2    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 NMS13.6      Summary13.6.1    Choosing an appropriate animal model and getting it approved takes time!13.6.2    Animal experiments are expensive and time-consuming13.6.3    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