Date Approved

8-26-2021

Graduate Degree Type

Thesis

Degree Name

Engineering (M.S.E.)

Degree Program

School of Engineering

First Advisor

Dr. Wael Mokhtar

Second Advisor

Dr. Mehemet Sozen

Third Advisor

Dr. Ryan Krauss

Academic Year

2020/2021

Abstract

Drug delivery is the most important factor of many therapies, but a lack of technology and research have led to a very generalized understanding of drug kinetics. Insulin pump therapy for the treatment of Type 1 Diabetes depends on precise delivery of the hormone into the adipose region between the dermis and underlying muscle. The kinetics of insulin within the adipose tissue environment is not well understood and varies greatly case to case. The use of computation fluid dynamics (CFD) models to study insulin kinetics in relation to influential factors will lead to a better understanding of the characteristics of insulin infusion.

Previously published studies revealed a single study using CFD to analyze insulin delivery, which indicated CFD research of insulin delivery was viable, but also needed more development for a complete biological computational model to simulate insulin delivery. Other studies have presented research in many of the key areas needed to create such a CFD model incorporating interstitial adipose tissue fluid flow and insulin delivery. Important characteristics were able to be identified from published research aiding in the development of an adipose tissue CFD model.

A porous media CFD model simulating the interstitial flow within adipose tissue was developed and modified to include insulin infusion in the model. The insulin deposition modeling was verified through the agreement with published study results. A study to analyze the effect of infusion set design and adipose tissue thickness on insulin deposition and dispersion was developed. This study considered the five most common cannula geometries currently on the market as well as adipose tissue thicknesses found across the body mass index range of patients, resulting in the parametric analysis of twenty-five cases.

Through the use of both graphic and statistical analysis, the results of the study indicated that both the cannula design and adipose tissue thickness have a significant effect on deposition and dispersion of insulin. Further, there was a clear difference between the thin adipose tissue and thick adipose tissue insulin deposition and dispersion observed. It was also found that as the lower angle cannulas decreased the dispersion of insulin within the tissue, but the cannula length at these infusion angles did not significantly impact the deposition and dispersion of insulin. In conjunction with previous understanding of insulin kinetics, the results indicated using a similar cannula geometry in lean and thick adipose tissue would result in largely different drug absorption characteristics. Further there would likely be a large variation in the insulin kinetics even within a singular patient due to adipose tissue thickness deviation.

Therefore, further research in the area of insulin kinetics with relation to the cannula design and tissue thickness is highly warranted, especially with autonomous insulin pumps already on the market. The best way to further improve insulin treatment would be to achieve a more precise delivery and absorption across each adipose environment within a singular patient’s anatomy. This study proved the use of computational models such as CFD is a very useful technology for such research in insulin delivery, but additional studies are required to further utilize computational models to enhance the understanding of insulin delivery kinetics within adipose tissue and the different factors effecting it.

Available for download on Saturday, August 27, 2022

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