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
220.127.116.11 In-vitro - importance of choosing suitable cell lines
18.104.22.168 adding the complexity of in-vivo background while keeping the simplicity of in-vitro
22.214.171.124 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
126.96.36.199 In-vitro and ex-vivo are mostly “closed” systems, but not absolutely
188.8.131.52 What is an “open” system?
184.108.40.206 Attempts to isolate open systems
13.1.3 Layers of complexity of in-vivo systems
220.127.116.11 Human cells in nude mice – a mixture of in-vitro and in-vivo
18.104.22.168 “Model” small animal systems
22.214.171.124 better model larger animal systems
13.2 Circulation time and biodistribution
13.2.1 factors affecting circulation time
126.96.36.199 "stealth layer" coating
188.8.131.52 zeta potential in-vivo in varying environments
184.108.40.206 filtration and excretion
13.2.2 where do the NMS go in-vivo?
220.127.116.11 checking the obvious organs (liver, spleen, kidney, blood…)
18.104.22.168 finding NMS in tissues and organs
22.214.171.124.2 within dissected tissue sections
126.96.36.199.3 in blood (ex-vivo versus in-vivo flow cytometry)
188.8.131.52.4 what is excreted?
13.2.3 Circulation time and dose optimization
184.108.40.206 measure drug concentration over time
220.127.116.11 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
18.104.22.168 direct measurement of restoration of lost or compromised functions
22.214.171.124 indirect measures of disease effects (e.g. behavior, weight gain/loss, .)
13.5.4 Some examples of in-vivo work with NMS
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
- 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)
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1083 BME, Purdue University, West Lafayette, IN