Transdermal drug carriers: Basic properties, optimization and transfer efficiency in the case of epicutaneously applied peptides

Abstract

In order to get across the intact mammalian skin, drug carriers must pass through a series of very fine pores with a diameter of typically less than 50 nm, under the influence of a suitable transdermal gradient. Well-known agent carriers, such as liposomes, fail to do this owing to their large (minimum) size. Special, composite carrying bodies called TransfersomesTM, achieve this goal by virtue of their very high and self-optimizing deformability. (The efficiency of passage for 500-nm Transfersomes through pores of 100 nm diameter is as high as that of pure water, 1500 times smaller than the former.) When applied onto the intact skin surface non-occlusively, Transfersomes penetrate the skin permeability barrier spontaneously. Subsequently, they are distributed, probably via the lymphatic system, throughout the whole body. Drug exchange between the Transfersomes and the biological surroundings may occur at this or any later stage. This permits regio-selective drug delivery by means of Transfersomes. (Topically applied corticosteroids, for example, can be confined to the viable skin with an efficiency of 99.999%.) Meticulous optimization ensures the Transfersome-mediated flux of lipids to exceed 0.1 mg cm-2 h-1, in the murine test system. Inulin, which has a low propensity for the association with Transfersomes, is carried across the skin less efficiently (10-20%). In spite of this, comparable serum values are measured 7 h after the epicutaneous or subcutaneous application of this compound in the form of Transfersomes. Combinations of peptides and Transfersomes provide a very successful means, however, for the non-invasive therapeutic use of such large molecular weight drugs on the skin. Transfersome-associated insulin is carried across the skin with an efficacy of ≥ 50% (and often ≥ 80%), for example; human trials with a number of preparations and formulations have proven this. The results measured with insulin are claimed to be representative of all substances with high encapsulation efficacy into and/or association capability with Transfersomes. © 1995.