The Systems Biology of COVID-19 and the SARS-CoV-2 virus. The class will build a foundation that includes the emergence of complexity, simple biological subsystems, their reductionist and equivalent toy and organ-chip models, and the measurements required to specify model architecture and parameters. Applications to biology, physiology, medicine, chemical and biological defense, pharmacology, drug discovery, and toxicology. UGrad: PHYS 240 01 and BME 290B; Grad: PHYS 326 and BME 395C.
Monday, April 2, 2012
Asgn_24A_Class_33_Article_20_2012_04_04
Read Article 20: Nicolas Bertrand and Jean Christophe Leroux. The journey of a drug-carrier in the body: An anatomo-physiological perspective. Journal of Controlled Release In press. DOI: 10.1016/j.jconrel.2011.09.098, 2012. (RefID20179). Get an overview of the content and be prepared to discuss each figure in detail. Post a PCRC.
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Ayeeshik Kole
ReplyDeleteAsgn_24A/PKPD (Journey of a drug-carrier)
0. Knew: Drug-carriers come in many shapes and sizes. The circulation time for each drug varies.
1. Learned: The physical properties of a CDC are very key in determining the physiological effects of how long it will circulate and where it will get stuck. The blood is extremely important in determining CDC behavior.
2. Pressing Question: How closely do we have to mimic immune functions of the blood? It seems like the complement system is highly interactive with CDCs. Can a system like Milli be able to test novel therapeutics (nanomedicine) without detailed spatial and immune design?
3. Presentation: Commercial Nanotherapeutics (Abraxane, etc.)
4. Thoughts: This article was a good review and very relevant to our PK/PD scaling discussions. The physiochemical parameters of each organ presented have pivotal roles in each step of the drug "journey." The article also does a good job of emphasizing how these drug distributions vary in animal models, giving Milli more support.
Brian Evans
ReplyDelete24A/Drug-carrier journey
0. Knew: I was familiar with most of the barriers to micro and nano drug-carriers in the body. I was familiar with the physiology of all organs except the spleen. I also knew that drug-carrier shape and size can be exploited to target certain tissues in the body.
1. Learned: Albumin deposition can protect carriers from opsonization, albeit trasiently due to Vroman Effect. PEG can cause pseudo-allergic reactions. Learned about ABC effect and that PEG enhances it. Finally, I learned that WBCs/neutrophils can release bactericidal entanglements of DNA and proteins called NETs (so WBCs and neutrophils act as spiderman of the circulatory system).
2. Pressing ?: Have people made a spleen on a chip? Should its function be considered in the design of milli 1.0?
3. Presentation: Stealth drug-cerrier design
4: Thoughts: I appreciated the logical flow to the article and the broad base of information it provided. I agree that it helped reinforce ideas and challenges that we have discussed earlier in terms of PK/PD properties of OoCs and HoCs.
Will Matloff
ReplyDelete24A/Journey of a Drug Carrier
0. Knew: The role of the blood in the pharmacokinetics of CDCs.
1. Learned: Very small changes in drug carriers can have significant effects in how it travels through the body. White blood cells have an important effect on CDCs.
2. Pressing?: Does the immune system primarily alter the pharmacokinetics of a drug or CDC, or does it also have a significant effect on the pharmacodynamics?
3. Presentation: Colloidal drug carriers.
4. Thoughts: The physical restraints of HoCs, such as tubing size, can make them unable to predict the exact PK/PD of certain CDCs.
Erica Curtis
ReplyDeleteAsgn_24A/PKPD Journey of a drug-carrier
0. Knew: Circulation time of drug carriers depends greatly on size, shape, and surface chemistry.
1. Learned: Understanding the complex interactions between drug carriers and blood components is perhaps the most vital step in a mechanistic approach to PK/PD modeling.
2. Pressing Question: Does this mean we need to include cell components in our blood substitute to mimic the immune responses there? What about matching in vivo architecture? We can't seem to get the hollow fibers small enough.
3. Presentation: Barriers to Novel Drug Carrier Testing On-Chip
4. Thoughts: The article was clear and concise, yet extremely informative. Despite the focus on CDCs, the article was a great introduction to PKPD considerations for Milli
Zach Eagleton
ReplyDeleteAsgn_24A/PKPD Journey of a drug-carrier
0 Knew: Various Physiological mechanisms of drug clearance.
1 Learned: The various geometries and chemistries of drug-delivery CDCs and the effect it has on when and where a drug is eliminated.
2 Pressing ?: Could milli be used to test drug delivery systems?
3 Presentation: Albumin and its functions.
4 Thoughts: I think this article was a good physiolocial overview of the bodies clearance mechanisms and how they relate to drug delivery. Goes along great with our project of OoC.
Lucas Hofmeister
ReplyDeleteAsgn_24A/PKPD Journey of a drug-carrier
0. Knew: basic drug clearance and delivery barriers
1. Learned: RES is a misnomer
2. Pressing ?: how does this relate to Fissell's most recent glomerular filtration editorial (http://www.ncbi.nlm.nih.gov/pubmed/22323639)
3. Presentation: opsonization
4. Thoughts: Great overview. This paper had a bunch of stuff that i wasnt familiar with!
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