Abstract
Skin is easily accessible for transdermal drug delivery and also attractive for biomarker sampling. These applications are strongly influenced by hydration where elevated hydration generally leads to increased skin permeability. Thus, favorable transdermal delivery and extraction conditions can be easily obtained by exploiting elevated skin hydration. Here, we provide a detailed in vivo and in vitro investigation of the skin hydration dynamics using three techniques based on electrical impedance spectroscopy. Good correlation between in vivo and in vitro results is demonstrated, which implies that simple but realistic in vitro models can be used for further studies related to skin hydration (e.g., cosmetic testing). Importantly, the results show that hydration proceeds in two stages. Firstly, hydration between 5 and 10 min results in a drastic skin impedance change, which is interpreted as filling of superficial voids in skin with conducting electrolyte solution. Secondly, a subtle impedance change is observed over time, which is interpreted as leveling of the water gradient across skin leading to structural relaxation/changes of the macromolecular skin barrier components. With respect to transdermal drug delivery and extraction of biomarkers; 1 h of hydration is suggested to result in beneficial and stable conditions in terms of high skin permeability and extraction efficiency.
Highlights
Skin is accessible for transdermal drug delivery and attractive for biomarker sampling
For transdermal drug delivery and non-invasive sampling to be successful, the drug or the biomarker has to pass the outermost layer of the epidermis, the stratum corneum (SC), which forms the main barrier of the skin[3]
The degree of skin hydration can be regulated by application of a topical formulation where the skin becomes hydrated either by water supplied as a formulation ingredient or as an endogenous by-product from transepidermal water loss (TEWL) when the formulation occludes the skin surface[19]
Summary
Skin is accessible for transdermal drug delivery and attractive for biomarker sampling. A drastic increase of the dynamics of molecular segments found in the keratin filaments was observed between 80 and 85% relative humidity; from a completely rigid keratin structure to a structure with both solid and mobile parts of the keratin filaments[20,31] In line with this finding, that hydration leads to increased keratin mobility, Norlén et al concluded that the dimensions of SC pieces swell about 26% in thickness and 4% in width when comparing the dry state with a hydrated state (i.e., after 90 min soaking in pure water) by employing a CLSM (confocal laser scanning microscopy) m ethod[27]. Another interesting characteristic of fully hydrated skin is the presence of intercellular aqueous inclusions (i.e., aqueous pools of varying sizes) in the SC, which have been observed in several studies utilizing different microscopy techniques[23,24,25,29]
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