TRANSDERMAL DRUG CARRIERS - BASIC PROPERTIES, OPTIMIZATION AND TRANSFER EFFICIENCY IN THE CASE OF EPICUTANEOUSLY APPLIED PEPTIDES

In order to get across the intact mammalian skin, drug carriers must p ass through a series of very fine pores with a diameter of typically l ess 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 call ed Transfersomes(TM), achieve this goal by virtue of their very high a nd 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 distribute d, 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 d elivery 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 f lux 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 Transfer somes, is carried across the skin less efficiently (10-20%). In spite of this, comparable serum values are measured 7 h after the epicutaneo us or subcutaneous application of this compound in the form of Transfe rsomes. Combinations of peptides and Transfersomes provide a very succ essful means, however, for the noninvasive therapeutic use of such lar ge molecular weight drugs on the skin. Transfersome-associated insulin is carried across the skin with an efficacy of greater than or equal to 50% (and often greater than or equal to 80%), for example; human tr ials 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 associatio n capability with Transfersomes.