701 Investigation of the absorption of allantoin in vitro skin models to support wound healing
JOURNAL OF INVESTIGATIVE DERMATOLOGY(2017)
摘要
Allantoin has been investigated in wound healing in formulations with minimal or unknown dermal penetration properties. We investigated the percutaneous absorption of the novel proprietary SD-101 cream (containing 0.5%-9.0% allantoin) and vehicle in 5 in vitro models: (1) barrier-free to simulate delivery directly to the capillary bed; (2) unabraded porcine; (3) abraded porcine to simulate compromised skin; (4) intact (full thickness) human; and (5) dermis-only human to mimic loss of skin barrier function due to broken skin. Creams were tested on human cadavers and porcine donors mounted in chambers designed to maintain skin in typical in vivo conditions. Samples were collected from the solution bathing the inner surface of the skin about 2, 4, 8, 12, 24, 32, and 48h after application and analyzed using HPLC with UV and MS detection. There was evidence of allantoin absorption in all models. Absorption was lowest in intact human skin. Absorption increased with higher concentrations of allantoin in the dermis-only human model, and uptake between the barrier-free and dermis-only human model was similar. The mean±SE absorption (μg) of 6% allantoin after 48h was 41.57±8.43 in the intact human model, 109.52±39.31 in the abraded porcine model, and 1990.40±167.34 in the dermis-only human model, and after 24h was 1348.30±201.39 in the barrier-free model. Allantoin absorption in the dermis-only human model was slow (≈8h), suggesting a long skin exposure time. Separate preclinical studies (with up to 9.0% allantoin) indicated no systemic absorption. In summary, allantoin is absorbed by the intact stratum corneum which may reduce wound formation. When damaged, as in wound models, skin absorption of allantoin increased significantly. Such findings support further investigation of SD-101 for the potential to treat wounds in a clinical setting.
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关键词
allantoin,wound healing,skin models,absorption
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