Development of In Vitro Isolated Perfused Porcine Skin Flaps for Study of Percutaneous Absorption of Xenobiotics
Abstract
This report describes an in vitro alternative animal model for dermatology and cutaneous toxicology. An anatomically intact, viable, isolated perfused skin preparation would be a useful model for studying percutaneous drug absorption because venous and arterial perfusate concentrations could be assessed independently of confounding systemic processes. A single-pedicle, axial-pattern, island-tubed skin flap was created in crossbred Yorkshire weanling pigs in one surgical procedure, then transferred 2 or 6 days later to a perfusion chamber for 10-12 hour studies. The development of this two stage surgical procedure is fully described. Pig skin was used because of its recognized similarity to human skin. Viability was assessed by glucose utilization, lactate production, and an absence of significant concentrations of the intracellular enzyme lactate dehydrogenase in the perfusate. Light and electron microscopy was used to develop a morphological viability index and to differentiate degenerative lesions from normal surgery or perfusion changes or lesions from exogenously applied toxins. Based on these criteria, biochemically viable skin flaps could be maintained for 12 hrs without significantly abnormal morphology. The research resulted in a reproducible perfusion model optimized for the xenobiotic absorption studies to be conducted in the second year. This preparation would be an humane alternative animal model for studies in cutaneous toxicology, physiology, oncology, and percutaneous drug absorption and metabolism.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1985
- Accession Number
- ADA183508
Entities
People
- J. E. Riviere
- K. F. Bowman
- N. A. Monteiro-riviere
Organizations
- North Carolina State University