title: Modelling Transdermal Drug Delivery and Drug Transport in the Viable Skin
Creators: name: Calcutt, Joshua J
Publisher: name: Griffith University
Year: 2021
Subjects: subject: Viable skin transport
subject: transdermal drugs
subject: vasculature network

description: Viable skin transport is critical to consider when applying transdermal drugs. Predicting concentration in the viable skin is highly essential for both toxicological and therapeutic reasons. The concentration is also vital for drugs that target topical relief of skin diseases. Furthermore, the viable skin has a significant impact on solutes that are highly lipophilic and have low molecular weight. In these cases, the viable epidermis may even become the rate-limiting barrier. Enhancement of transdermal techniques and a better understanding of drug physiochemistry has also enhanced other drug's ability to permeate through the stratum corneum The second chapter, Chapter 2, highlighted the need for further modelling of the viable skin by performing a literature review. Within the study, the previous methods of modelling the vasculature were described. From the analysis, it was seen that the implementation of a sink condition or the use of a distributed elimination model was insufficient to estimate the impact of the capillary network. Therefore, it was concluded that to get a better representation of experimental data; the capillary loops had to be considered more explicitly. The central research question of this thesis was the impact the vasculature network had on drug transport within the viable skin. However, micropora- tion of the skin and its effect on drug transport was the second research ques- tion. Chapter 3 investigated the latter case by considering drug transport after the stratum corneum had been microporated. A three-dimensional model was developed, and the different impact micropore parameters had on transport was identified. Capillary loops were then introduced into the model. The shape and size of the loops were varied to determine if they affected the transport profile. Furthermore, the effect of changing the ratio of capillary loops to pores or the recruitment of the capillary loops was identified. The capillary loop model developed in Chapter 3 was enhanced in Chapter 4. The chapter aimed to determine the role the capillary loops play in viable skin transport. The different capillary loop parameters were investigated, and their impact on a homogenous model's effective depth of a sink condition was identified. The new capillary model's concentration profile was also compared to experimental data and the most prevalent mathematical models. From the results, the new capillary model was much more effective at estimating the Econazole concentration. However, it failed to account for the plateauing of concentration in the deeper dermal regions. Chapter 5 enhanced the modelling in the previous chapter by considering the blood ow and permeability barrier of the capillary loop. The permeability barrier was assumed on the surface of the capillary loops and represented the endothelial lining. The results of incorporating these two variables produced a more accurate estimation of dermal transport. The enhanced model was able to estimate the plateauing trend evident in both Hydrocortisone and Econazole. The chapter also discussed the importance of considering a dispersion coefficient instead of a diffusion coeffcient. Finally, the transient profile of the model was five-fold faster than previous mathematical models, which matched the seven-fold increase in experimental data. Chapter 6 further investigated the vasculature network by modelling the subpapillary plexus. However, in this model, the plexus was not modelled explicitly and instead generalised through the introduction of one compartment. The one-compartment generalisation gave an estimation for the subpapillary plexus. When the plexus was introduced, a much higher concentration for the deeper dermal region was evident. The impact of different parameters associated with the plexus was also analysed. The capillary models developed in previous chapters were compared, and the strengths and limitations of each model were identified. However, the modelling of the plexus was preliminary and needs further investigation in the future. Chapter 7 looked at using compartments to estimate the concentration after microporation. A three-dimensional approach was developed to determine concentration. Compartments were utilised as they provided a more straightforward solution than the previous chapters. They also require significantly less computational power. The accuracy of the approach was determined by comparing the model to the Comsol model developed in Chapter 3. From the comparison, a reasonable estimation of concentration was evident when a sufficient number of compartments were employed. Furthermore, the computational time required to solve the system decreased significantly when the compartment approach was applied.