An in vitro Skin Penetration Model for Compromised Skin: Estimating Penetration of Polyethylene Glycol [14C]-PEG-7 Phosphate

BACKGROUND/AIMS: Establishing dermal penetration rates is important to better understand the safety of topically applied materials, especially for premature infant skin with compromised skin barrier function. Skin prematurity involves thinner stratum corneum and underdeveloped epidermis/dermis resulting in decreased barrier function, higher transepidermal water loss and greater chemical penetration, when compared to healthy full-term neonate/adult skin. METHODS: We developed an in vitro skin penetration model using human ex vivo skin to estimate penetration for premature/compromised skin barrier conditions by tape stripping. Skin barrier deficiency was characterized by transepidermal water loss. Baby wipe lotion containing 5 mg/cm(2) [(14)C]-PEG-7 phosphate was applied 5 times to human skin samples of intact, moderately or highly compromised skin barrier and once at 25 mg/cm(2) over 24 h. RESULTS: Overall penetration of [(14)C]-PEG-7 phosphate was low (<5%) even for highly compromised skin. The absorption rate was higher (p < 0.001) for compromised skin versus intact skin. No significant difference was seen between moderately and highly compromised skin by repeated dosing. Under single-dose conditions, penetration through highly compromised skin was significantly higher compared to intact skin (p = 0.001). CONCLUSION: Our model demonstrates that even under highly compromised skin conditions, penetration of [(14)C]-PEG-7 phosphate is low (<5%) and only 4-6 times higher compared to mature/intact skin and does not approach 100%. Penetration was unaffected by single or multiple dosing conditions.