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I am working on developing a PBPK model for liposomic nanoparticles used to deliver drugs to fells in the bloodstream. However, I do not have any in vivo data or in vitro data. Given only chemical and physical properties like pKa or the octanol-water partition coefficient, how can a get a relatively accurate estimate of the tissue:blood partition coefficient, as well as the renal & metabolic clearance?

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  • $\begingroup$ What is your overall goal or research question that you would like to answer? We could collaborate on a research project. $\endgroup$
    – Polymania
    Nov 4, 2016 at 16:02
  • $\begingroup$ @Polymania that would be great! How can I contact you? This has to do with modeling liposomic nanoparticles binding to cells that flow through the blooddtream. I want to estimate thr concentration of the cell-lipsosome complex in various compartments of the body, so I am trying to model the systems seperately for now. However, there is not much in vivo sata for both the cells and the nanoparticles, although I do have a little data on the cells. Hence, I need to estimate these parameters. I am new to PBPK modeling so i am not sure if this approach is suitable for my project. $\endgroup$
    – TanMath
    Nov 4, 2016 at 18:40
  • $\begingroup$ @Polymania I have saved your email. I will send an email as soon as possible. $\endgroup$
    – TanMath
    Nov 4, 2016 at 18:52

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Regarding the tissue partition coefficient, Li et al. said: "By using such a parameter, it is assumed that there is the same transfer kinetics of nanoparticles from blood into tissues as from tissues back into blood circulation, and an equilibrium of concentrations between blood and tissue exists. These assumptions may not be appropriate for nanoparticles."

  1. Physiologically Based Pharmacokinetic Modeling of Nanoparticles Mingguang Li, Khuloud T. Al-Jamal, Kostas Kostarelos, and Joshua Reineke ACS Nano 2010 4 (11), 6303-6317 DOI: 10.1021/nn1018818

However if you are set on using a tissue:blood partition coefficient (Kp), Yun and Edginton have done a review of 6 in silico methods for determining Kp for small molecules. You may be able to extrapolate to nanoparticles.

  1. Yun, Y.E., Cotton, C.A. & Edginton, A.N. J Pharmacokinet Pharmacodyn (2014) 41: 1. doi:10.1007/s10928-013-9342-0

Finally, if you are looking for data to help determine a partition coefficient, there is an excellent review of liposomal doxorubicin pharmacokinetic data in animals and humans here.

  1. Gabizon, A., Shmeeda, H. & Barenholz, Y. Clin Pharmacokinet (2003) 42: 419. doi:10.2165/00003088-200342050-00002
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  • $\begingroup$ Do you work with PBPK models of liposomes? $\endgroup$
    – TanMath
    Aug 18, 2017 at 4:45

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