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<p><b>Drug Delivery Across the Skin </b> </p> <p align="left">G. Cevc<br> Medizinische Biophysik, Klinikum r.d.I., Technische Universitüt München<br> Ismaningerstr. 22, D-81675 München, Germany, E.U. </p> <p align="left"><b>Experts Opinion in Investigational Drugs 6: 1887-1937 (1997).</b></p> <p align="left">Since the introduction of the first through the skin (TTS) therapeutic in 1980, a total of 34 TTS products were brought to the market and numerous drugs were tested for their suitability for such delivery. Most are small, owing to the tightness of the skin barrier, which must be overcome. This barrier resides in the outermost skin layer, the stratum corneum. It is of mechanical, anatomical, as well as chemical nature: laterally overlapping cell multi-layers are sealed with the tightly packed, intercellular lipid multi-lamellae. Chemical skin permeation enhancers increase the transport across the barrier by partly solubilising or extracting the skin lipids and by creating hydrophobic pores in the organ. This is often irritating and not always well tolerated by the consumers. TTS approach allows small drugs (< 400 Da) to permeate through the resulting pores in the skin, with a short lag-time and subsequent period of steady state. Drug bioavailability for TTS delivery is typically below 50 %, without first pass effect. To get wider, hydrophilic channels one must porate the skin: by a small electric current (< 0.4 mA/cm^2) across the skin (iontophoresis) or therapeutic ultrasound (few W/cm^2; sonoporation). High-voltage (> 150 V, electroporation) opens the skin wider and less reversibly. Each standard poration method requires experience and gadgets to operate, and is not generally applicable: at best, it can deliver charged/small molecules (< 4000 Da) efficiently across the skin. The potential harm of gadget-driven skin poration is tolerated to extend the window of opportunity beyond that of conventional TTS patches and especially to deliver polypeptides across the skin. Lipid based drug carriers (liposomes, niosomes, nanoparticle microemulsions, etc.) were proposed as an alternative, low risk solution to the problem of limited delivery across the skin barrier. Such suspensions may provide an improved drug reservoir on the skin but the aggregates remain confined to the surface. The main action of conventional carrier suspensions is to increase the skin hydration and/or to shed molecules into the organ which behave as skin permeation enhancers. An exception are the specially designed, highly deformable carriers, Transfersomes. Such recently developed carriers comprise pharmaceutically acceptable, established compounds and were proposed to penetrate the skin barrier along the naturally occurring transcutaneous moisture gradient. Transfersomes appear to be guided into the hydrophilic (virtual) channels in the skin, which they reversibly widen after non-occlusive administration. Small and large, hydrophobic and hydrophilic molecules are deliverable across the stratum corneum after association with Transfersomes, drug distribution after skin passage probably proceeding via the lymph. This results in quasi-zero order kinetics and significant systemic drug levels after a lag-time of up to a few hours. The relative efficiency of skin crossing by Transfersomes is typically above 50 %, with some possibility for the regional drug targeting being provided.</p> <p><a href="index.html"><----</a> | <a href="../.././index.html" target="_top" onmouseover="putstattext('Was ist das Besondere an IDEA?'); return true;">Startseite</a> | <a href="../../about-us/index.html" target="_top" onmouseover="putstattext('Über die Geschichte, die Leute, die Zusammenarbeiten und die Zukunftspläne von IDEA.'); return true;">Über uns</a> | <a href="../../corporate_factsheet/index.html" target="_top" onmouseover="putstattext('Corporate Factsheet'); return true;">Corporate Factsheet</a> | Wissenschaft | <a href="../../publications/index.html" target="_top" onmouseover="putstattext('Publikationen'); return true;">Publikationen</a> | <a href="../../product_opportunities/index.html" target="_top" onmouseover="putstattext(''); return true;">Einsatzmöglichkeiten</a> | <a href="../../financial/index.html" target="_top" onmouseover="putstattext('Investoren und grundlegende finanzielle Daten.'); return true;">Finanzierung</a> | <a href="../../press_releases/index.html" target="_top" onmouseover="putstattext('Originaltexte...'); return true;">Pressemitteilungen</a> | <a href="../../latest_newsletter/index.html" target="_top" onmouseover="putstattext('IDEAS letzter ausgegebene Newsletter'); return true;">Letzter Newsletter</a> | <a href="../../press_clippings/index.html" target="_top" onmouseover="putstattext('IDEA in der Presse - die Originaltexte.'); return true;">Pressespiegel</a> | <a href="../../conferences/index.html" target="_top" onmouseover="putstattext('Bei diesen Veranstaltungen treffen sie uns, und wir können uns persönlich unterhalten...'); return true;">Konferenzen</a> | <a href="../../career/index.html" target="_top" onmouseover="putstattext('Wir suchen Talente mit Engagement und bieten im Gegenzug viel.'); return true;">Karriere</a> | <a href="../../contact/index.html" target="_top" onmouseover="putstattext('Wir freuen uns, von Ihnen zu hören!'); return true;">Kontakt</a> | <a href="../../faq/index.html" target="_top" onmouseover="putstattext('Der Unterschied zwischen Liposomen und Transversomen, Produktverträglichkeit und vieles mehr.'); return true;">Wissenschaftliche FAQ</a> | <a href="../../glossary/index.html" target="_top" onmouseover="putstattext(''); return true;">Glossar</a> | <a href="../../sitemap/index.html" target="_top" onmouseover="putstattext('Schaffen Sie sich einen Eindruck von IDEA.'); return true;">Seitenübersicht</a> | <a href="../../search/index.html" target="_top" onmouseover="putstattext('Finden Sie Dokumente in dieser Seite über Schlagwörter---'); return true;">Suchen</a> |  </p>