TRANSFERSOMES-MEDIATED TRANSEPIDERMAL DELIVERY IMPROVES THE REGIO-SPECIFICITY AND BIOLOGICAL-ACTIVITY OF CORTICOSTEROIDS IN-VIVO

Innovative, carrier-based suspensions of several commonly used cortico steroids are introduced. These formulations contain the recently devel oped agent carriers, transfersomes, which are sufficiently deformable to penetrate into or across the intact skin barrier. The resulting dru g delivery can be varied systematically: depending on the precise appl ication conditions and carrier design, between 100% and less than or e qual 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 rela tive area under the curve for the blood pool below a few per cent, at most, of that resulting from the corresponding drug injection. Transfe rsomes hence improve the specificity of topical drug delivery and the overall drug safety. Increasing the total applied drug dose, as well a s the dose per area, promotes the systemic drug availability. After an epicutaneous application of sufficient drug amount, therapeutically m eaningful agent concentration is reached in the blood. This normally h appens after the lag time of approximately 4 h to 6 h. When hydrocorti sone, dexamethasone, or triamcinolone-acetonide are administered epicu taneously 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 t he 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 subcutaneou s injection of (3-10X) lower amounts of the same drug. Concentration o f the epicutaneously administered corticosteroids in the blood is alwa ys 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 s everal times lower than that currently used in the dermatic formulatio ns for the treatment of skin diseases. The biological anti-edema activ ity of transfersomal corticosteroid formulations hence exceeds that of the corresponding commercial products, probably owing to the superior drug-targeting potential in the organ.