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<p><b>Anti-inflammatory effects of Cu,Zn-Superoxide dismutase in Transfersomes, micelles or liposomes, in the acute murine ear oedema model. </b> </p> <p align="left">S.I. Simões*, M. B. F. Martins*, M. E. M. Cruz*, G. Cevc+</p> <p align="left">*UNFAB, Department of Biotechnology, IBQTA, Instituto Nacional de Engenharia e Tecnologia Industrial, Estrada do Paço do Lumiar, 1699 Lisboa Codex, Portugal;<br> +Medical Biophysics, Klinikum r.d.I., The Technical University of Munich, Ismaningerstr. 22, D-81675 München, Germany </p> <p align="left"><b>In: <i>Proceedings of Control Release Society Satellite Meeting in Lisbon, 1998</i>.</b></p> <p align="left">Superoxide radicals are involved in a variety of pathologic situations, such as ischemia-reperfusion injury, inflammation and radiation damage. Cu,Zn-Superoxide-dismutase (Cu,ZnSOD), with known antioxidant and anti-inflammatory properties, has been suggested as therapeutic agent for treating such conditions. However, this enzyme has a very short half-live in the bloodstream. Frequent injections are therefore required to maintain therapeutic drug concentration in the blood, which results in poor patient compliance and in oscillating systemic concentration levels. Recently, there has been increased interest in drug administration via the skin, both for the local treatment of the diseased skin (topical delivery) and for systemic therapy (transdermal delivery). However, to reach these goals one must achieve good efficiency of protein transport across the skin. Composite, ultradeformable drug carriers, Transfersomes, were argued to deliver small as well as large molecules through the skin. Via the lymph, the epicutaneously delivered material can also reach the blood circulation. This was observed with the specially optimised lipid mixtures in the form of vesicles (often comprising phospholipids and detergents) after non-occlusive percutaneous administration. The process is believed to be driven by the transepidermal water activity gradient. This can push sufficiently hydrophilic entities through the skin barrier, if the penetration resistance is small enough due to the high flexibility of the complex vesicles membranes. Properly designed Transfersomes used as carriers can ensure the efficiency of drug transfer across the skin, and the resulting biodistribution, to resemble that achieved by subcutaneous injections. The effects of topically applied Cu,Zn-SOD on local inflammation were investigated in the acute murine ear oedema model. Ear swelling was induced by topical application of arachidonic acid (=AA, 2 mg in EtOH/ear). Edema-suppression by the epicutaneously applied Cu,Zn-SOD associated with Transfersomes, corresponding mixed micelles, or liposomes was measured, using empty vehicles as negative controls for each group. Positive reference groups were treated epicutaneously with several low molecular weight nonsteroidal anti-inflammatory agents. Of all carriers tested, only the enzyme-loaded Transfersomes (60 µg SOD/kg) reduced the swelling of ears significantly, by (73±10) %. Aqueous enzyme solution had no such effect. Indomethacin (3 mg/kg), etofenamate (30 mg/kg) and piroxicam (3 mg/kg) reduced the oedema by (83±7) %, (64±3) % and (40±10) %, respectively. Microscopic evaluation of haematoxylin and eosin-stained histological sections, prepared from the formalin-fixed ears, confirmed that Cu,Zn-SOD-loaded Transfersomes reduce the local tissue inflammation. The fact that untreated ears or the tissues treated with the empty carriers revealed much stronger epidermal hyperplasia and infiltration of inflammatory cells corroborates such conclusion. The acute model of inflammation based on AA has a limited value for determining the mechanism of drug action. This test is generally accepted, however, for studying the anti-inflammatory action of drugs in the first stage trials. Our results are therefore encouraging but further investigations with chronic models should establish the potential usefulness of Cu,Zn-SOD in Transfersomes for proper inflammation therapy.</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> | <a href="../../science/index.html" target="_top" onmouseover="putstattext('Wissenschaftliche Kooperationen, Veröffenlichungen usw.'); return true;">Wissenschaft</a> | Publikationen | <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>