Development of a Rat Model to Investigate Contributions of Anatomic and Physiologic Determinants of in Vivo Skin Permeation
Abstract
The skin is a heterogeneous, bi-directional impediment to chemical flux, in which the stratum corneum is a major, though not the sole, rate-limiting barrier layer to permeation. Systemic toxicity following dermal exposure to environmental chemicals and use of skin as a portal for systemic administration of drugs have led to extensive investigations of the inward flux of xenobiotics applied to the outer surface of skin. Those investigations mainly utilized in vitro experimental systems that were limited by the absence of normal physiologic functions. Heretofore, only a few, complex in vivo models have been reported for the study of contributions of cutaneous physiology, especially skin capillary permeability and blood flow, to the cutaneous permeation of xenobiotics. The objective of the present research was to investigate an in vivo skin permeation model system that was sensitive to perturbations of skin capillary physiology and stratum corneum. A "fuzzy" rat model system was devised that employed outward cutaneous migration of a systemically administered permeation probe, isoflurane. Specially devised, transdermal vapor collection devices were used to capture the outward flux of isoflurane through the skin. Isoflurane flux measurements, coupled with blood isoflurane concentrations, were used to calculate cutaneous permeability coefficients (Kp) of isoflurane, as an index of permeation, under various conditions of normal or perturbed cutaneous physiologic states. Physiologic perturbations were performed to test the sensitivity of the model system to detect effects of minoxidil-mediated vasodilation, phenylephrine-mediated vasoconstriction, and leukotriene D4-mediated increased capillary permeability on the outward flux of isoflurane. Tape stripping and topical ether-ethanol application produced either physical removal or chemical disruption of the stratum corneum, respectively.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 30, 1991
- Accession Number
- AD1010993
Entities
People
- Nicholas M. Fleischer
Organizations
- Uniformed Services University of the Health Sciences