The isolated perfused human skin flap model: A missing link in skin penetration studies?

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• 作者：Selenia Ternullo^a ; ^{selenia.ternullo@uit.no} ; Louis de Weerd^b ; ^c ; ^{Louis.De.Weerd@unn.no} ; G&oslash ; ril Eide Flaten^a ; ^{goril.flaten@uit.no} ; Ann Mari Holsæ ; ter^a ; ^{ann-mari.holsater@uit.no} ; Nata&scaron ; a &Scaron ; kalko-Basnet^a ; ^{natasa.skalko-basnet@uit.no}
• 关键词：CM ; Cellophane membrane ; CLSM ; confocal laser scanning microscopy ; DIRT ; dynamic infrared thermography ; FDC ; Franz diffusion cells ; HS ; human skin ; IR ; infra red ; IPHSF ; isolated perfused human skin flap ; KHb ; modified Krebs-Henseleit buffer ; PS ; pig skin ; PG ; propylene glycol ; SC ; stratum corneum
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：96
• 期：Complete
• 页码：334-341
• 全文大小：1034 K
• 卷排序：96

文摘

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 6 h 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 (pH 7.4). 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 6 h 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.