Enhancement of skin permeation of fluorescein isothiocyanate-dextran 4 kDa (FD4) and insulin by thermalporation.

ABSTRACT

Thermalporation has gained attention as a physical means to enhance skin permeation by creating micropores in the primary skin barrier, stratum corneum, which allows much higher permeation of middle and high molecular weight biopharmaceuticals. In the present study, a PassPort® system (PS) was used as a thermalporation device, and the obtained change in permeation resistance of drugs was evaluated using a parallel skin permeation-resistance model. In addition, the blood concentration-time profile after topical application of insulin was also investigated with the PS treatment. Fluorescein isothiocyanate-dextran (FD-4) and insulin were used as model middle molecular weight drugs. Micropores created by the PS treatment were measured using an optical microscope. An in vitro skin permeation and an in vivo pharmacokinetics experiments were done with FD-4 and insulin, respectively. Barrier function recovery after the PS treatment was evaluated with changes in the electrical skin resistance. About 960-fold higher skin permeation of FD-4 was observed by PSs treatment (4 milliseconds (ms), 200 micropores/cm2). A gradually increased blood concentration of insulin was observed by the PSs treatment, and the relative bioavailability of insulin was 21.1% compared with subcutaneous injection. Skin resistance value was dramatically decreased immediately after the PS treatment, but its value was turned into the initial one by 12 h. The thermalporation is effective for improving skin permeation of FD-4 and transdermal absorption of insulin. These results suggested that the PS treatment may be utilized to increase the skin permeation of topically applied FD-4 and insulin.