Team:NJU China/Modeling

Pharmacokinetics is the quantitative study of the drug absorption, distribution and metabolism within the body. It shows the fluctuation of the drug concentration within a certain part of the body along the time. For a new drug, we need to first experimentally obtain the pharmacokinetic parameters and then make the pharmacokinetic model to predict the concentration change after drug administration. Thus pharmacokinetic model plays a vital role in new drug development. Since our targeting-exosome is a brand new drug delivery system, we need to make a pharmacokinetic model to check if it can really target the specific site we want and predict the concentration change within that site.

A.Exosome concentration change over time within each compartment

Figure.2 Exosome concentration change along the time in different compartments.


As we can see from the figure.2, the concentration of exosomes in the blood falls down along the time while the concentration of exosomes in the peripheral compartment goes up first then falls down. Comparing the concentration change of exosomes over time in the liver(our target organ) with other tissues, we can easily see that the peak concentration of exosomes in liver is much higher than that of non-target tissues. Thus we can assure that the after add the liver targeting protein to the exosome (the percentage of exosomes get into the liver increases), the concentration of exosomes in the liver greatly outnumber that in other tissues.

B.The relationship between the exosome concentration change over time and absorption percentage in liver.

Figure.3 exosome concentration change over time with different absorption percentage in liver


The difference of exosome distribution between liver and other tissues lie in that the absorption percentage of exosomes in liver is much higher than that in other tissues. After plot concentration change over time and absorption percentage in 3D(Figure.3),we can see that as the absorption percentage increases, the peak of drug concentration also goes up. To achieve higher concentration in liver, we can make outside modification to exosomes to direct more exosomes into the liver.

C.The relationship between the exosome concentration change over time and drug half-life.

Figure.4 exosome concentration change over time with different exosome halflife in liver


Encapsulate the siRNA into exosomes can great increase the half-life of the siRNA, and via outside modification we can change the half-life of the exosome. As we can see from Figure.4 , after the drug half-life increases, the concentration falls more slowly so that the drug can function more time in the target tissue.


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