| Drugs and chemicals applied to the skin surface permeate deeper tissue layers, and also pass into the body's systemic circulation by entering blood vessels in the dermis. Quantitative aspects of the dermal diffusion and capillary clearance processes are key to the effective development of transdermally delivered drugs, as well as to risk assessment of chemical exposure in applications ranging from cosmetics and other consumer products, to protection against biological warfare agents. The present work addresses three major aspects of these phenomena:; A comprehensive macroscopic transient model of transdermal diffusion is developed (Chaps. 3 and 4). It specifically accounts for the spatial distribution of blood vessels (in terms of convection-enhanced volumetric dispersion and clearance coefficients), and explicitly incorporates transport through deeper tissue. Comparisons with published experimental results show the manner in which the model improves upon existing models.; The first steps toward the development of a microscopic model of the dermis are presented (Chap. 5). The model is based on dermal physiology, and it will encompass physical processes such as protein binding and hindered diffusion of solute. The end result will be a framework for correlating and predicting the effective “background” transport properties (solute diffusivity and partition coefficient) of the dermis, within the context of the medium in which blood vessels and appendages are embedded.; A new geometrical model is developed to describe the dermal capillary clearance process (Chaps. 6 and 7). The real physiological structure is modeled in terms of a doubly periodic array of absorbing capillaries. Convection-dominated transport in the blood flow within is coupled with diffusion outside, the latter process being quantified using a slender-body-theory approach. Convective transport across the capillary wall and in the surrounding interstitial space is also considered. The model accounts for the finite permeability of the capillary wall, as well as for the geometry of the capillary array, based on realistic values of physiological parameters. The ultimate outcome is a prediction of the dermal flux (or rate of absorption) per unit area of skin. Parametric studies quantify the importance of the capillary permeability and blood flow velocity in the process of the microvascular clearance. |
