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<p><b>Ultradeformable Lipid Vesicles Can Penetrate the Skin and other Semi-Permeable Barriers Intact. Evidence from Double Label CLSM Experiments and Direct Size Measurements</b> </p> <p align="left"> Gregor Cevc, Andreas Schaetzlein, Holger Richardsen</p> <p align="left">The stability of various aggregates in the form of lipid bilayer vesicles was tested by three different methods before and after crossing different semi-permeable barriers. First, polymer membranes with pores significantly smaller than the average aggregate diameter were used as the skin barrier model. The dynamic light scattering was employed to monitor vesicle size changes after barrier passage for several lipid mixtures with different bilayer elasticity. The conclusion is that vesicles change their size and/or shape, dependent on bilayer stability and elasto-mechanics, to overcome an otherwise confining pore. The change is transient and only involves vesicle shape and volume adaptation in the case of mixed lipid aggregates with highly flexible bilayers (Transfersomes®). Such ultradeformable vesicles retain their size before and after pore penetration unless they are torn apart by shear. This is remarkable in light of the very strong aggregate deformation during the enforced barrier passage. Simple phosphatidylcholine vesicles with less flexible bilayers lack a comparable capability and stability. Conventional liposomes are therefore fractured during the transport through a semi-permeable barrier. As reported by other researchers before, such vesicles are fragmented to the size of a narrow pore if a sufficient pressure is applied across the barrier; otherwise, liposomes clog the barrier. The precise outcome depends on the trans-barrier flux and/or on relative vesicle vs. pore size. Lipid vesicles applied on the skin behave accordingly. Mixed lipid vesicles penetrate the skin if they are sufficiently deformable. If this is the case, they cross inter-cellular constrictions in the organ without a significant composition or size modification. To prove this we labelled vesicles with two different fluorescent markers and applied the suspension on intact murine skin without occlusion. The confocal laser scanning microscopy of the skin then revealed a practically indistinguishable distribution of both labels in the stratum corneum, corroborating the first assumption. To confirm the second postulate we compared the vesicles size in the starting suspension and in the blood after non-invasive transcutaneous aggregate delivery. Size exclusion chromatograms of sera from the mice that received ultradeformable vesicles on the skin were undistinguishable from the results measured with the original vesicle suspension. Taken together the results support our previous postulate that ultradeformable vesicles penetrate the skin intact, that is, without permanent disintegration.</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>