The isolated perfused porcine skin flap as an in vitro model for percutaneous absorption and cutaneous toxicology.
The isolated perfused porcine skin flap (IPPSF) is a new perfused skin model which allows in vitro cutaneous pharmacology and toxicology studies to be conducted in a viable skin preparation which has a normal anatomical structure and a functional microcirculation. The purpose of this review is to (1) outline the background of this field which indicated the need for this type of model; (2) outline the surgical procedures needed to create and harvest viable preparations; (3) overview the criteria (biochemical, physiological, and histological) used to assess viability during an experiment; (4) present results of percutaneous absorption, cutaneous metabolism, transdermal delivery (passive and active), and skin distribution experiments conducted to date; (5) present the strategy developed to quantitate percutaneous absorption and cutaneous drug distribution using compartmental and physiological-based pharmacokinetic models; (6) assess the correlation of IPPSF data to in vivo results; (7) define the biochemical, physiological and histological (LM, TEM, enzyme histochemistry) response of the IPPSF to topically applied cutaneous vesicants; (8) overview where this type of in vitro model fits into the overall framework of cutaneous toxicology and pharmacology research; and (9) outline possible paths for future development. This review should provide the reader with an appreciation of some unique problems in this field which require an in vitro model that is closely integrated in structure and function to the in vivo setting.
Riviere
J E
JE
Cutaneous Pharmacology and Toxicology Center, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Monteiro-Riviere
N A
NA
D000818:Animals; D066298:In Vitro Techniques; D012867:Skin / Q000473:pathology; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D012871:Skin Diseases / Q000139:chemically induced* / Q000473:pathology; D012879:Skin Physiological Phenomena; D013552:Swine