Dermal patches consisting of cultured human skin with
antibiotics, which have a protective effect on
wound skin as well as a preventative effect on second
infection of the skin, were prepared and mathematically analyzed as a new drug delivery system (DDS) that can be applied to serious skin defects such as severe
burns. In the present study, a three-dimensional cultured human skin model (living skin equivalent-high, LSE-high) was used as a cultured skin membrane and
tetracycline HCl (TC-HCl) and
chloramphenicol (CP) were used as
antibiotics. At first,
antibiotics were entrapped in the LSE-high from the dermal side through culture medium in order to obtain a drug-loaded LSE-high. The
antibiotic release from the drug-loaded LSE-high was then examined and the resulting release data were used to calculate the effective diffusion coefficient of the
antibiotics (D(LSE)) and initial loading concentration of the
antibiotics (C0) in the LSE-high. The release profile of TC-HCl was represented by general diffusion-limited kinetics, whereas an initial burst effect was found in the release profile of CP. Therefore, the burst effect was taken into account for analyzing the release profile of CP. Stripped skin excised from hairless rats was used as a
wound model, and the
antibiotic permeation through the skin from aqueous
solution was examined and evaluated using differential equations for Fick's second law of diffusion to obtain the effective diffusion coefficient of the
antibiotics in the
wound skin (D(skin)). Furthermore, the
antibiotic permeation profile through the excised stripped skin from the drug-loaded LSE-high was measured and theoretically evaluated by Fick's second law of diffusion with previously obtained parameters (C0, D(LSE), D(skin)) using a newly constructed two- or three-layered diffusion model. The calculated concentrations of TC-HCl and CP in the upper epidermis of the model
wound skin were over their minimum inhibitory concentration (MIC) for several hours against various bacteria, suggesting that this dosage system is useful for the treatment of severe
burns. In addition, the present analytical method and diffusion model, with the drug-loaded LSE-high and stripped rat skin, are useful tools for evaluating this new DDS.