IMPEDANCE-BASED ASSESSMENT OF SKIN BARRIER STABILITY UNDER FIXATION, STRESSORS, AND PROTECTIVE TREATMENTS IN A FRANZ CELL SETUP

Sammanfattning

Transdermal drug delivery is extensively studied due to possibility for drugs to bypass first-pass metabolism and provide a non-invasive route for administration. However, the use of skin in Franz cell experiments, a common method for studying drug permeation, often faces challenges such as skin degradation over time, which can affect the reliability of permeability studies. This study investigated how chemical fixation (glutaraldehyde and formaldehyde), surfactantstress (sodium dodecyl sulfate), chaotropic agents (urea), and mechanical stress (sonophoresis) influence the electrical and structural integrity of the stratum corneum (SC). Using electrochemical impedance spectroscopy (EIS) in a Fanz diffusion cell system, time-resolved measurements of membrane resistance (R2), capacitance (Q1), and dispersion exponent (n1) were used to quantify barrier function and dielectric behavior under controlled conditions.Fixation with glutaraldehyde (2.5%) significantly enhanced SC resistance, suppressed capacitance, and maintained dielectric uniformity, confirming covalent crosslinking and structural stabilization. In contrast, formaldehyde (2.5%) produced weaker and less durable fixation, with increased susceptibility to aqueous and mechanical stress. SDS exposure caused concentration-dependent barrier collapse; 1 M SDS caused rapid R2 collapse and increased Q1 and n1, though GA fixation partially mitigated this effect. Urea (8 M) caused gradualdegradation probably via protein destabilization. Sonophoresis induced mechanical disruption of the SC structure through cavitation and mechanical stress, particularly in unfixed and FA-fixed samples. Notably, the introduction of GA during ultrasound application led to accelerated fixation and enhanced R2, suggesting a synergistic effect of ultrasound- enhanced crosslinking.These results demonstrate that glutaraldehyde fixation provides superior structuralreinforcement compared to formaldehyde, and that sonophoresis can be used strategically to enhance fixation or permeation, and that EIS is a sensitive tool for tracking SC responses to physiochemical and mechanical stress. The findings support optimized fixation strategies for barrier preservation and the design of stable in vitro skin models for transdermal research.