title: The isolated perfused human skin flap model: A missing link in skin penetration studies?
abstract: Development of effective (trans)dermal drug delivery systems requires reliable skin models to evaluate skin drug penetration. The isolated perfused human skin flap remains metabolically active tissue for up to 6h during in vitro perfusion. We introduce the isolated perfused human skin flap as a close-to-in vivo skin penetration model. To validate the model's ability to evaluate skin drug penetration the solutions of a hydrophilic (calcein) and a lipophilic (rhodamine) fluorescence marker were applied. The skin flaps were perfused with modified Krebs-Henseleit buffer (pH7.4). Infrared technology was used to monitor perfusion and to select a well-perfused skin area for administration of the markers. Flap perfusion and physiological parameters were maintained constant during the 6h experiments and the amount of markers in the perfusate was determined. Calcein was detected in the perfusate, whereas rhodamine was not detectable. Confocal images of skin cross-sections shoved that calcein was uniformly distributed through the skin, whereas rhodamine accumulated in the stratum corneum. For comparison, the penetration of both markers was evaluated on ex vivo human skin, pig skin and cellophane membrane. The proposed perfused flap model enabled us to distinguish between the penetrations of the two markers and could be a promising close-to-in vivo tool in skin penetration studies and optimization of formulations destined for skin administration.
authors.affiliation: Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø The Arctic University of Norway, Universitetsveien 57, 9037 Tromsø, Norway. Electronic address: selenia.ternullo@uit.no.
authors.forename: Selenia
authors.initials: S
authors.lastname: Ternullo
authors.affiliation: Department of Plastic and Reconstructive Surgery, University Hospital of North Norway, Sykehusvegen 38, 9019 Tromsø., Norway; Department of Clinical Medicine, University of Tromsø The Arctic University of Norway, Universitetsveien 57, 9037 Tromsø, Norway. Electronic address: Louis.De.Weerd@unn.no.
authors.forename: Louis
authors.initials: L
authors.lastname: de Weerd
authors.affiliation: Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø The Arctic University of Norway, Universitetsveien 57, 9037 Tromsø, Norway. Electronic address: goril.flaten@uit.no.
authors.forename: Gøril Eide
authors.initials: GE
authors.lastname: Flaten
authors.affiliation: Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø The Arctic University of Norway, Universitetsveien 57, 9037 Tromsø, Norway. Electronic address: ann-mari.holsater@uit.no.
authors.forename: Ann Mari
authors.initials: AM
authors.lastname: Holsæter
authors.affiliation: Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø The Arctic University of Norway, Universitetsveien 57, 9037 Tromsø, Norway. Electronic address: natasa.skalko-basnet@uit.no.
authors.forename: Nataša
authors.initials: N
authors.lastname: Škalko-Basnet
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D005452:Fluoresceins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D009924:Organ Culture Techniques; D010477:Perfusion / Q000379:methods*; D012235:Rhodamines / Q000378:metabolism / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D013524:Surgical Flaps / Q000502:physiology*; D013552:Swine
chemical_list: D005452:Fluoresceins; D012235:Rhodamines; C007740:fluorexon
keywords: Human skin; Isolated perfused human flap; Skin models; Skin penetration; Skin therapy