Transfersomes-mediated transepidermal delivery improves the regio-specificity and biological activity of corticosteroids in vivo

Innovative, carrier-based suspensions of several commonly used corticosteroids are introduced. These formulations contain the recently developed agent carriers, transfersomes, which are sufficiently deformable to penetrate into or across the intact skin barrier. The resulting drug delivery can be varied systematically: depending on the precise application conditions and carrier design, between 100% and less than or equal to 5% of applied drug is deposited in the outermost skin region. Low area dose favors the drug retention in the skin and keeps the relative area under the curve for the blood pool below a few per cent, at most, of that resulting from the corresponding drug injection. Transfersomes hence improve the specificity of topical drug delivery and the overall drug safety. Increasing the total applied drug dose, as well as the dose per area, promotes the systemic drug availability. After an epicutaneous application of sufficient drug amount, therapeutically meaningful agent concentration is reached in the blood. This normally happens after the lag time of approximately 4 h to 6 h. When hydrocortisone, dexamethasone, or triamcinolone-acetonide are administered epicutaneously in transfersomes, for example, at the dose of 1.5 mg/kg, 1.5 mg/kg, and 1 mg/kg, the respective concentrations of these drugs in the blood at t=8 h are approximately 0.4 mu g/ml, near 0.75 mu g/ml and 0.007 mu g/ml. These results are comparable to those of a subcutaneous injection of (3-10X) lower amounts of the same drug. Concentration of the epicutaneously administered corticosteroids in the blood is always lower than in the skin, whereas 28 mu g/g, 156 mu g/g, and 10 mu g/g are found for the above mentioned drug doses at t=8 h, respectively. Transfersome-based corticosteroids are biologically active at doses several times lower than that currently used in the dermatic formulations for the treatment of skin diseases. The biological anti-edema activity of transfersomal corticosteroid formulations hence exceeds that of the corresponding commercial products, probably owing to the superior drug-targeting potential in the organ.