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From 2012.igem.org

Contents 1 Human Body Model 2 Explanation of the model 2.1 General mass balance equations for all the VLPs 2.2 General mass balance equations for the unbound VLPs 2.3 General mass balance equations for the medicine 3 Case study 3.1 Introduction 3.2 Parameters 3.3 Results 3.4 Discussion/Conclusion 4 Remarks 4.1 Important parameters 4.2 Possibilities of the model 4.3 Receptor / Affinity database 4.4 Future work / MoSCoW

Human Body Model

Human body model introduction

Why do we have this human model

Explanation of the model

Our model is constructed in such a way that each compartment of the model represent an organ or multiple organs with the same physical properties. We decided to have separate compartments for the kidneys, liver, lungs and the intestine. All other organs are grouped in the rapid or slowly perfused tissue. In the case study we made a new compartment between the intestine and the liver to represents the intestine tumor. (figure: flow scheme human body)

(figure: flow scheme human body)

In our model we’ve used three different mass balance equations for an organ. The first mass balance describes the concentration of all the VLPs in the organ, this is to see the overall change in the VLP concentration. The second mass balance equation describes the concentration of the unbound VLPs. This is because the unbound particles can move freely into the body while the bound particles stays into the organ. (figure: flow scheme organ) The final mass balance equation is for the concentration of the medicine in the organ. With these three mass balance equation we’ve developed our model

(figure: flow scheme organ)

General mass balance equations for all the VLPs

The equations below describe the change in concentration of all the VLPs in the different organs. The mass balances for the different organs consists out of multiple parts. Each organ as at least an flow that describes the concentration of VLPs that come into the organs and a flow that describes the VLP concentration that goes out of the organ. Also each organ has a rate of decay incorporated into the mass balance to describe the falling apart of the VLPs in the different organs. The mass balance of the kidney has also an equation for the removal of the VLPs via the urinal track.

(Equations)

General mass balance equations for the unbound VLPs

Besides needing an equation to describe the change in concentration of all the VLPs, we also need an equation to describe the change in concentration of the unbound VLPs for each organ. The mass balances for the different organs consists out of multiple parts. The mass balances are similar to the mass balance for all the VLPs, with a slight difference, it’s has a rate of VLP attachment. This rate describes the attachment of the VLPs onto the surface of the cell.

(Equations)

General mass balance equations for the medicine

The last set of mass balances are for the change of concentration of the medicine in the different organs. These equations consists out of multiple parts, similar to the previous set of mass balances. Each organ as at least an flow that describes the concentration of medicine that come into the organs and a flow that describes the medicine concentration that goes out of the organ. Also each organ has a rate of decay incorporated into the mass balance to describe the decay of medicine in the different organs. The mass balance of the kidney has also an equation for the removal of the medicine via the urinal track.

(Equations)

Case study

Introduction

Fluorouracil for colon cancer

Parameters

For the distribution of VLPs throughout the human body, used parameters were obtained from the documentation Slovenia 2012 or from literature sources [1]. The estimated parameters for the organs in table XXX are explained as followed: Blood-flow, the amount of blood in liters flushing throughout the organs, Volumes, the size of the organ, Receptor, the concentration of receptors in µM and the partition coefficient of the medicine that is packaged within the VLP.

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Organ	Blood-flow [L/min]	Volume [L]	Receptor 1 [uM]	Partition coefficient medicine
Slowly perfused tissue	2.12	53.2	0.237	100
Rapidly perfused tissue	1	3.61	0.237	100
Kidney	1.06	0.31	0.237	100
Liver	1.4	1.82	0.237	100
Lung	5.58	0.56	0.237	100
Intestine Healthy	0.94	4.41	0.237	100
Tumor	0.1	0.49	10.716	100
Arterial	5.58	1.7	0.237	100
Venous	5.58	3.9	237	100

Parameters that were estimated for non organ variables are found in table 2 and are explained as followed. Affinity constant for receptor, is the binding affinity of the VLPs to the receptor on the cell surface. VLP elimination rate is the half-life of the VLPs. VLP Renal removal rate is the removal rate of the VLPs within the kidneys. Medicine elimination rate is the removal/degradation of the medicine within the human body. The last parameter is the packaging constant which encapsulate the amount of medicine in µmol? within a single VLP.

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Affinity constant for receptor	0.001
VLP elimination rate	0.000143
VLP Renal removal rate	0.000403
Medicine elimination rate	0.05
Packaging constant	300

Results

Mark/Jasper

Discussion/Conclusion

Mark/Jasper

Remarks

Important parameters

1. Ratio of receptor concentration between tumor and healthy cells 2. Distribution of receptors on cell surface 3. Stability of the VLP 4. Packaging quantity of the VLP 5. Binding affinity of the VLP to the receptor 6. Medicine absorption of tumor / healthy cells

Possibilities of the model

Receptor / Affinity database

Future work / MoSCoW

References Benjamin L. Shneider; Sherman, Philip M. (2008). Pediatric Gastrointestinal Disease. Connecticut: PMPH-USA. pp. 751.