In Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device

The study developed a simulation model using the finite element method to investigate how mechanical stretch and hypobaric pressure affect the diffusion of large molecules into the skin. The model was validated against in-vitro experiments. Results showed that skin stretching and thinning occurred, with a 20%-26% increase in hair follicle diameter and a 21%-27% reduction in skin thickness. However, the concentration of dextrans in the stratum corneum remained below the detection limit, regardless of hypobaric pressure, and concentrations in the viable epidermis and dermis were unaffected. Notably, permeation into the receptor fluid was significantly enhanced under hypobaric pressure, increasing from below detection limit to up to 6 μg/cm^2. The in-silico simulations aligned well with experimental results, especially when diffusion coefficients were increased under hypobaric pressure. The study concludes that while mechanical enlargement of hair follicles does not fully explain the increased permeation, hypobaric pressure likely enhances diffusion in the skin, improving transdermal drug delivery.