This thesis investigates the potential for monitoring current and historic blood serum concentrations of amino acids via transdermal extraction using phenylalanine as a case study. This work furthers the ﬁeld of non-invasive monitoring of amino acid disorders which have several advantages over invasive methods such as blood tests. In this thesis we derive models to simulate blood serum concentrations, the formation of the skin reservoir and, ﬁnally, transdermal extraction of amino acids under an applied electric ﬁeld.Chapter 1 concerns itself with the biological background and sets up motivation of the thesis by discussing amino acids, associated amino acid disorders, the overarching clinical problem, skin structure and transdermal extraction methods. Chapter 2 then considers mathematical techniques utilised throughout the thesis.Chapter 3 formulates a model for the distribution of phenylalanine in blood serum. One compartment and two compartment approaches are considered in both a fasting state and a non-fasting state. We consider if these have a noticeable eﬀect on the blood serum concentration of phenylalanine.Having obtained a model for the distribution of phenylalanine in blood serum, chapter 4 models the formation of reservoirs of amino acids in the skin. Prior work has identiﬁed the existence of such a reservoir, but its formation has not been addressed. The models developed consider the eﬀect of the removal of outer layers of skin, the stratum disjunctum, and production of amino acids in the skin. Unknown parameters are estimated by comparing the model to in vivo and in vitro data.Chapter 5 and 6 are concerned with transdermal extraction under an applied electric ﬁeld. Chapter 5 formulates the velocity induced by applying an electric ﬁeld across a charged interface. Chapter 6 utilises these results for modelling extraction of compounds through the skin under an applied electric ﬁeld.
|Date of Award||26 Apr 2017|
|Sponsors||Biotechnology and Biological Sciences Research Council|
|Supervisor||Jane White (Supervisor) & Richard Guy (Supervisor)|
- Reverse iontophoresis
- Transdermal delivery
- amino acid